Pest control agent

ABSTRACT

Specific amine derivatives have been found to possess excellent activities as pest control agents.

This applications is a Divisional of U.S. application Ser. No.13/814,753, filed Feb. 7, 2013; which is a 371 of PCT/JP2011/069352,filed Aug. 26, 2011; which claims priority based on Japanese PatentApplication No. 2010-194584 filed Aug. 31, 2010; the contents of all ofwhich are incorporated herein by reference in their entirety.

TECHNICAL FIELD

The present invention relates to novel amine derivatives and pestcontrol agents which use the same.

BACKGROUND ART

Many pest control agents have been discovered to date. However, stillnovel pesticides are desired today owing to, for example, the resistantproblem to pesticides and to concerns such as the persistence of thepesticide effects and safety at the time of use.

In paddy rice cultivation in East Asia and Southeast Asia in particular,as indicated in Non-Patent Document 1, damage by planthoppers which havedeveloped chemical resistance to major insecticides, includingneonicotinoids such as imidacloprid and phenylpyrazole pesticides suchas fipronil has emerged. As a result, specific agents for planthoppersthat have developed resistance are awaited.

With regard to heterocycle-containing amine derivatives, Patent Document1 describes monoalkylamine compounds having a cyano group on thenitrogen atom, and the insecticidal activity of such compounds onaphids. However, no specific disclosure is made concerning dialkylaminecompounds, nor is anything mentioned about the control activity on pestsother than aphids.

Patent Document 2 mentions amine derivatives which contain a2,6-dichloro-4-pyridyl group and have a carboxyl group on the nitrogenatom, as well as the fungicidal activities and insecticidal activitiesthereof, but discloses no other heterocycles.

In Non-Patent Documents 2 and 3, amine derivatives which contain a6-chloro-3-pyridyl group and have an acetyl group on the nitrogen atomare disclosed as metabolites or reaction intermediates, but no mentionis made of their pest control activities. Non-Patent Document 4discloses amine derivatives which contain a 6-chloro-3-pyridyl group andhave on the nitrogen atom a N-methylcarbamoyl group or aN-formylcarbamoyl group, but makes no mention of the pest controlactivities thereof.

Patent Document 3 discloses a plurality of compounds having ringstructures similar to those of compounds of formula (Ie), but these areintended for use as herbicides; no mention is made of pest control.

Patent Document 4 discloses the structural formula ofN-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamide(Table 1, Compound No. 3 in Patent Document 4), but discloses nothingwhatsoever concerning the method of preparation. Nor is this compoundincluded in the lists of compounds for which pest control activitieswere observed (Tables 2 and 3 in Patent Document 4).

Patent Document 5 discloses the structural formula ofN-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamide(Table 7, Example No. 12 in Patent Document 5), but discloses nothingwhatsoever concerning the method of preparation. Nor is this compoundmentioned in the examples of compounds having pest control activitieswhich are described in the working examples.

Non-Patent Document 5 discloses a plurality of compounds having ringstructures similar to the compounds of subsequently mentioned formula(Ie), but these are merely disclosed as synthesis intermediates.

Patent Document 6 discloses a plurality of compounds having ringsstructures similar to the compounds of formula (Ie), but no mention orsuggestion is made concerning compounds having a trifluoroacetic acidimino structure.

CITATION LIST Patent Literatures

-   [PL 1] Japanese Unexamined Patent Application Publication No.    2003-26661 (JP 2003-26661 A)-   [PL 2] International Publication No. WO 2002/050035 (WO 2002-050035)-   [PL 3] European Unexamined Patent Application Publication No. 432600-   [PL 4] Japanese Unexamined Patent Application Publication No. Hei    5-78323 (JP 5-78323 A)-   [PL 5] European Unexamined Patent Application Publication No. 268915-   [PL 6] European Unexamined Patent Application Publication No. 259738

Non Patent Literatures

-   [NPL 1] Pest Management Science, 64(11), 1115-1121 (2008)-   [NPL 2] Journal of Agricultural and Food Chemistry, 58(4), 2419    (2010)-   [NPL 3] Pest Management Science, 61(8), 742 (2005)-   [NPL 4] Journal of Photochemistry and Photobiology B: Biology,    98(1), 57 (2010)-   [NPL 5] Chemische Berichte, 88, 1103-8 (1955)

SUMMARY OF INVENTION Technical Problem

It is therefore an object of the present invention to provide novel pestcontrol agents and thereby, in the pest control field, to solve theproblems of existing pesticides, such as resistance to the pesticides,persistence of the pesticide effects, and safety at the time of use.

One major object of the invention is to provide pesticides which haveexcellent control effects against the brown rice planthopper, thewhite-backed rice planthopper and the small brown planthopper, all majorinsect pests today in the field of paddy rice cultivation, which have ahigh activity even against pesticide-resistant planthoppers, and whichreduce the chances for the exposure of workers to the pesticide duringuse in, for example, soil treatment, seed treatment and seedling boxtreatment and can thus be safely employed.

Solution to Problem

The inventors have conducted extensive investigations in order to solvethe above problems, as a result of which they have discovered that aminederivatives of chemical formula (I) have excellent activities as pestcontrol agents.

Accordingly, the invention provides:

(1) A pest control agent comprising at least one compound of thefollowing formula (I) or a salt thereof

(wherein Ar is a phenyl group which may be substituted or a 5- or6-membered heterocycle which may be substituted;

R₁ is a hydrogen atom or a C₁₋₆ alkyl group;

R₂ is a C₁₋₆ alkylcarbonyl group in which the alkyl moiety may besubstituted with a halogen atom, a C₁₋₆ alkyloxycarbonyl group in whichthe alkyl moiety may be substituted with a halogen atom, a C₁₋₆alkylsulfonyl group in which the alkyl moiety may be substituted with ahalogen atom, CONR₆R₇, a C₁₋₆ O,O′-alkylphosphoryl group in which thealkyl moiety may be substituted with a halogen atom, a cyano group, aformyl group or a nitro group;

R₃ is a C₁₋₈ alkylene group which may be substituted with a halogenatom, a C₂₋₈ alkynylene group which may be substituted with a halogenatom, a C₂₋₈ alkynylene group which may be substituted with a halogenatom, a phenylene group which may be substituted, or a 5- or 6-memberedheterocyclic divalent group which may be substituted; and

R₄ is a hydrogen atom, a cyano group, a phenyl group which may besubstituted, a 3- to 8-membered cyclic alkyl group which may besubstituted, a 3- to 8-membered heterocyclic which may be substituted, ahalogen atom, OR₅, OCOR₅, OCOOR₅, COR₅, COOR₅, SR₅, SOR₅, SO₂R₅,N—CO—OR₈, N—CO—SR₈, N—CS—OR₈, N—CS—SR₈, N—O—CO—R₈, O—CO—R₈, O—CO—OR₈,O—CO—SR₈, O—CS—OR₈, O—CS—SR₈, S—CS—OR₈, S—CS—SR₈, S—CO—OR₈, S—CO—SR₈,S—CS—R₈, NR₉R₁₀, O—CO—NR₉R₁₀, O—CS—NR₉R₁₀, S—CO—NR₉R₁₀ or S—CS—NR₉R₁₀;

wherein R₅ is a C₁₋₆ alkyl group which may be substituted with a halogenatom, an aryl group which may be substituted with a halogen atom or anaralkyl group which may be substituted with a halogen atom;

R₆ and R₇ are each independently a hydrogen atom or a C₁₋₆ alkyl groupwhich may be substituted with a halogen atom;

R₈ is a C₁₋₆ alkyl group which may be substituted, the substituent beinga halogen atom, a C₁₋₄ alkyloxycarbonyl group, a C₁₋₄ alkylcarbonylgroup, a benzoyl group which may be substituted with a halogen atom or aC₁₋₄ alkyl group which may be substituted with a halogen atom, a C₁₋₄alkyloxy group or a C₁₋₄ alkylthio group;

R₉ and R₁₀ are each independently a hydrogen atom, a formyl group, aC₁₋₆ alkyl group which may be substituted with a halogen atom, a C₁₋₆alkylcarbonyl group in which the alkyl moiety may be substituted with ahalogen atom, a C₁₋₆ alkylcarbonyloxy group in which the alkyl moietymay be substituted with a halogen atom, a phenyl group which may besubstituted (the substituent being a halogen atom, a C₁₋₄ alkyl groupwhich may be substituted with a halogen atom, or a C₁₋₄ alkyloxy groupwhich may be substituted with a halogen atom), or a benzyl group whichmay be substituted (the substituent being a halogen, a C₁₋₄ alkyl groupwhich may be substituted with a halogen or a C₁₋₄ alkyloxy group whichmay be substituted with a halogen), R⁹ and R¹⁰ together form a ring anddenote a 3- to 10-membered heterocycloalkyl group containing at leastone nitrogen atom, or N, R₉ and R₁₀ together form a ring and denote a 5-or 6-membered aromatic heterocycle containing at least one nitrogenatom, and

N, R₂, R₃ and R₄ may together form a group of formula (E)

wherein Y is a hydrogen atom, a halogen atom, a hydroxyl group, a C₁₋₆alkyl group which may be substituted with a halogen atom, a C₁₋₆alkyloxy group which may be substituted with a halogen atom, a cyanogroup, a formyl group or a nitro group, and R_(4e) is a C₁₋₆ alkyl groupsubstituted with a halogen or a C₁₋₆ alkyloxy group which may besubstituted with a halogen;

with the proviso that if Ar is a 2,6-dichloro-4-pyridyl group, then R₂is not a C₁₋₆ alkyloxycarbonyl group in which the alkyl moiety may besubstituted with a halogen atom).

(2) The pest control agent according to (1), wherein Ar in formula (I)is a 6-chloro-3-pyridyl group or a 5-chloro-3-thiazolyl group.

(3) The pest control agent according to (1) or (2), wherein R₂ informula (I) is a C₁₋₆ alkylcarbonyl group in which the alkyl moiety maybe substituted with a halogen atom, a C₁₋₆ alkylsulfonyl group in whichthe alkyl moiety may be substituted with a halogen atom, or a cyanogroup.

(4) The pest control agent according to (1), wherein the compound offormula (I) is a compound of formula (Ie) below.

(5) The pest control agent according to (4), wherein R_(4e) in formula(Ie) is a C₁₋₆ alkyl group substituted with a halogen atom.

(6) The pest control agent according to (4), wherein Y in formula (Ie)is a hydrogen atom or a halogen atom.

(7) The pest control agent according to (4), wherein R_(4e) in formula(Ie) is a C₁₋₆ alkyl group substituted with a halogen atom, and Y is ahydrogen atom or a halogen atom.

(8) The pest control agent according to (4), wherein the compound offormula (Ie) is a compound selected from the group consisting ofN-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamide,N-[1-((6-chloro-5-fluoropyridin-3-yl)methyl)pyridin-2(1H)-ylidine]-2,2,2-trifluoroacetamide,N-[1-((6-fluoropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamide,N-[1-((6-bromopyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamide,N-[1-(1-(6-chloropyridin-3-yl)ethyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamide,N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2-difluoroacetamide,2-chloro-N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2-difluoroacetamide,N-[1-((2-chloropyrimidin-5-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamideandN-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,3,3,3-pentafluoropropanamide.

(9) The pest control agent according to any one of (1) to (8), which hasa pest control activity on at least one type of pest selected from thegroup consisting of lepidopterous pests, hemipterous pests,thysanopterous pests, dipterous pests, coleopterous pests, animalparasitic fleas and ticks, and canine heartworms.

(10) The pest control agent according to any one of (1) to (9), whereinthe pest is an agricultural/horticultural pest or an animal parasiticpest.

(11) The pest control agent according to any one of (1) to (9), whereinthe pest is a pesticide-resistant pest.

(12) An amine derivative of the following formula (I) or a salt thereof

(wherein Ar is a phenyl group which may be substituted or a 5- or6-membered heterocycle which may be substituted;

R₁ is a hydrogen atom or a C₁₋₆ alkyl group;

R₂ is a C₁₋₆ alkylcarbonyl group in which the alkyl moiety may besubstituted with a halogen atom, a C₁₋₆ alkyloxycarbonyl group in whichthe alkyl moiety may be substituted with a halogen atom, a C₁₋₆alkylsulfonyl group in which the alkyl moiety may be substituted with ahalogen atom, CONR₆R₇, a C₁₋₆ O,O′-alkylphosphoryl group in which thealkyl moiety may be substituted with a halogen atom, a cyano group, aformyl group or a nitro group;

R₃ is a C₁₋₈ alkylene group which may be substituted with a halogenatom, a C₂₋₈ alkenylene group which may be substituted with a halogenatom, a C₂₋₈ alkynylene group which may be substituted with a halogenatom, a phenylene group which may be substituted, or a 5- or 6-memberedheterocyclic divalent group which may be substituted; and

R₄ is a hydrogen atom, a cyano group, a phenyl group which may besubstituted, a 3- to 8-membered cyclic alkyl group which may besubstituted, a 3- to 8-membered heterocyclic which may be substituted, ahalogen atom, OR₅, OCOR₅, OCOOR₅, COR₅, COOR₅, SR₅, SOR₅, SO₂R₅,N—CO—OR₈, N—CO—SR₈, N—CS—OR₈, N—CS—SR₈, N—O—CO—R₈, O—CO—R₈, O—CO—OR₈,O—CO—SR₈, O—CS—OR₈, O—CS—SR₈, S—CS—OR₈, S—CS—SR₈, S—CO—OR₈, S—CO—SR₈,S—CS—R₈, NR₉R₁₀, O—CO—NR₉R₁₀, O—CS—NR₉R₁₀, S—CO—NR₉R₁₀ or S—CS—NR₉R₁₀;

wherein R₅ is a C₁₋₆ alkyl group which may be substituted with a halogenatom, an aryl group which may be substituted with a halogen atom or anaralkyl group which may be substituted with a halogen atom;

R₆ and R₇ are each independently a hydrogen atom or a alkyl group whichmay be substituted with a halogen atom;

R₈ is a C₁₋₆ alkyl group which may be substituted, the substituent beinga halogen atom, a alkyloxycarbonyl group, a alkylcarbonyl group, abenzoyl group which may be substituted with a halogen atom or a C₁₋₄alkyl group which may be substituted with a halogen atom, a alkyloxygroup or a C₁₋₄ alkylthio group;

R₉ and R₁₀ are each independently a hydrogen atom, a formyl group, aC₁₋₆ alkyl group which may be substituted with a halogen atom, a C₁₋₆alkylcarbonyl group in which the alkyl moiety may be substituted with ahalogen atom, a C₁₋₆ alkylcarbonyloxy group in which the alkyl moietymay be substituted with a halogen atom, a phenyl group which may besubstituted (the substituent being a halogen atom, a C₁₋₄ alkyl groupwhich may be substituted with a halogen atom, or a C₁₋₄ alkyloxy groupwhich may be substituted with a halogen atom), or a benzyl group whichmay be substituted (the substituent being a halogen, a C₁₋₄ alkyl groupwhich may be substituted with a halogen or a C₁₋₄ alkyloxy group whichmay be substituted with a halogen), R⁹ and R¹⁰ together form a ring anddenote a 3- to 10-membered heterocycloalkyl group containing at leastone nitrogen atom, or N, R₉ and R₁₀ together form a ring and denote a 5-or 6-membered aromatic heterocycle containing at least one nitrogenatom; and

if Ar is a pyridyl group which may be substituted or a pyrimidyl groupwhich may be substituted, N, R₂, R₃ and R₄ may together form a group offormula (E)

wherein Y is a hydrogen atom, a halogen atom, a hydroxyl group, a C₁₋₆alkyl group which may be substituted with a halogen atom, a C₁₋₆alkyloxy group which may be substituted with a halogen atom, a cyanogroup, a formyl group or a nitro group, and R_(4e) is a C₁₋₆ alkyl groupsubstituted with a halogen or a C₁₋₆ alkyloxy group which may besubstituted with a halogen;

with the proviso that if Ar is a 2,6-dichloro-4-pyridyl group, then R₂is not a C₁₋₆ alkyloxycarbonyl group in which the alkyl moiety may besubstituted with a halogen atom, and if Ar is a 6-chloro-3-pyridylgroup, then R₁ is not a hydrogen atom, Y is not a 5-methyl group andR_(4e) is not a CF₃ group).

(13) The amine derivative or a salt thereof according to (12), whereinAr in formula (I) is a 6-chloro-3-pyridyl group or a5-chloro-3-thiazolyl group.

(14) The amine derivative or a salt thereof according to (12) or (13),wherein R₂ in formula (I) is a C₁₋₆ alkylcarbonyl group in which thealkyl moiety may be substituted with a halogen atom, a C₁₋₆alkylsulfonyl group in which the alkyl moiety may be substituted with ahalogen atom, or a cyano group.

(15) The amine derivative or a salt thereof according to (12), whereinthe compound of formula (I) is a compound of formula (Ie′) below.

(wherein Ar′ is a pyridyl group which may be substituted or a pyrimidylgroup which may be substituted; Y is a hydrogen atom, a halogen atom, ahydroxyl group, a C₁₋₆ alkyl group which may be substituted with ahalogen atom, a C₁₋₆ alkyloxy group which may be substituted with ahalogen atom, a cyano group, a formyl group or a nitro group; and R_(4e)is a C₁₋₆ alkyl group substituted with a halogen or a C₁₋₆ alkyloxygroup which may be substituted with a halogen;

with the proviso that if Ar′ is a 6-chloro-3-pyridyl group, then R₁ isnot a hydrogen atom, Y is not a 5-methyl group and R_(4e) is not atrifluoromethyl group).

(16) The amine derivative or a salt thereof according to (15), whereinR_(4e) in formula (Ie′) is a alkyl group substituted with a halogenatom.

(17) The amine derivative or a salt thereof according to (15), wherein Yin formula (Ie′) is a hydrogen atom or a halogen atom.

(18) The amine derivative or a salt thereof according to (15), whereinR_(4e) in formula (Ie′) is a C₁₋₆ alkyl group substituted with a halogenatom and Y is a hydrogen atom or a halogen atom.

(19) The amine derivative or a salt thereof according to (15), whereinthe compound of formula (Ie′) is a compound selected from the groupconsisting ofN-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamide,N-[1-((6-chloro-5-fluoropyridin-3-yl)methyl)pyridin-2(1H)-ylidine]-2,2,2-trifluoroacetamide,N-[1-((6-fluoropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamide,N-[1-((6-bromopyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamide,N-[1-(1-(6-chloropyridin-3-yl)ethyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamide,N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2-difluoroacetamide,2-chloro-N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)^(ylidene]-)2,2-difluoroacetamide,N-[1-((2-chloropyrimidin-5-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamideandN-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,3,3,3-pentafluoropropanamide.

(20) The amine derivative or a salt thereof according to any one of (12)to (19), which has a pest control activity on at least one type of pestselected from the group consisting of lepidopterous pests, hemipterouspests, thysanopterous pests, dipterous pests, coleopterous pests, animalparasitic fleas and ticks, and canine heartworms.

(21) A method for controlling pests, comprising the step of using thepest control agent according to any one of (1) to (9) or the aminederivative or a salt thereof according to any one of (12) to (20).

(22) A method for controlling agricultural/horticultural pests,comprising the step of treating plant seeds, roots, tubers, bulbs,rhizomes, soil, a nutrient solution in hydroponics, a solid culturemedium in hydroponics, or a carrier for growing plants, with the pestcontrol agent according to any one of (1) to (9) or the amine derivativeor a salt thereof according to any one of (12) to (20), thereby inducingthe compound to penetrate and translocate into the plants.

(23) The method according to (21), wherein the pest is anagricultural/horticultural pest or an animal parasitic pest.

(24) The method according to (21), wherein the pest is apesticide-resistant pest.

Advantageous Effects of Invention

By using the amine derivatives of the invention, it is possible toeffectively carry out the control of the diamondback moth, the commoncutworm, aphids, delphacid planthoppers, thrips and many other pests.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a graph showing the results of powder x-ray diffractionanalysis on the crystals ofN-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamideprepared by a first preparation method.

FIG. 2 is a graph showing the results of differential scanningcalorimetry on the crystals ofN-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamideprepared by the first preparation method.

FIG. 3 is a graph showing the results of powder x-ray diffractionanalysis on the crystals ofN-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamideprepared by a second preparation method.

FIG. 4 is a graph showing the results of differential scanningcalorimetry on the crystals ofN-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamideprepared by the second preparation method.

FIG. 5 is a graph showing the results of differential scanningcalorimetry on the crystals ofN-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamideprepared by a third preparation method.

FIG. 6 is a graph showing the results of powder x-ray diffractionanalysis on the crystals ofN-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamideprepared by a fourth preparation method.

FIG. 7 is a graph showing the results of differential scanningcalorimetry on the crystals ofN-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamideprepared by the fourth preparation method.

FIG. 8 is a graph showing the results of differential scanningcalorimetry on the crystals ofN-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamideprepared by a fifth preparation method.

DESCRIPTION OF EMBODIMENTS

In the amine derivatives of chemical formula (I) which serve as theactive ingredients of the pest control agents provided by the invention,Ar is a phenyl group which may be substituted or a 5- or 6-memberedheterocycle which may be substituted, and is preferably a 5- or6-membered heterocycle which may be substituted.

Exemplary substituents include halogen atoms, C₁₋₄ alkyl groups whichmay be substituted with halogen atoms, alkyloxy groups which may besubstituted with halogen atoms, hydroxyl groups, cyano groups and nitrogroups. Halogen atoms and C₁₋₄ alkyl groups which may be substitutedwith halogen atoms are preferred.

Illustrative examples of phenyl groups which may be substituted includea phenyl group, a 3-chlorophenyl group, a 4-chlorophenyl group, a3-cyanophenyl group, a 4-cyanophenyl group, a 3-nitrophenyl group, a4-nitrophenyl group, a 3,5-dichlorophenyl group, a 4-methylphenyl group,a 4-methoxyphenyl group, a 3,5-dibromophenyl group, a 2,4-dibromophenylgroup, a 4-fluorophenyl group, a 4-bromophenyl group, a3-nitro-5-bromophenyl group and a 3,5-bistrifluoromethyphenyl group. A4-nitrophenyl group, a 4-cyanophenyl group or a 3,5-dibromophenyl groupis preferred.

Illustrative examples of 5- or 6-membered heterocycles which may besubstituted include pyridine, thiazole, tetrahydrofuran and furan.3-Pyridyl groups and 3-thiazolyl groups are preferred. A6-chloro-3-pyridyl group, a 5-chloro-3-thiazolyl group, a6-chloro-5-fluoro-3-pyridyl group, a 6-bromo-3-pyridyl group, a6-fluoro-3-pyridyl group, a 5,6-dichloro-3-pyridyl group or a6-trifluoromethyl-3-pyridyl group is more preferred. A6-chloro-3-pyridyl group, a 6-fluoro-3-pyridyl group, a6-chloro-5-fluoro-3-pyridyl group or a 6-bromo-3-pyridyl group isespecially preferred.

In chemical formula (I), the “C₁₋₆ alkyl group” represented by R₁ is analkyl group having from 1 to 6 carbons that is linear, branched, cyclicor a combination thereof. When a branched or cyclic alkyl group isincluded, it is apparent that the number of carbons is at least 3.Specific examples include a methyl group, an ethyl group, a propylgroup, an isopropyl group and a cyclopropyl group. A methyl group or anethyl group is preferred.

R₂ is a C₁₋₆ alkylcarbonyl group in which the alkyl moiety may besubstituted with a halogen atom, a C₁₋₆ alkyloxycarbonyl group in whichthe alkyl moiety may be substituted with a halogen atom, a C₁₋₆alkylsulfonyl group in which the alkyl moiety may be substituted with ahalogen atom, CONR₆R₇, a C₁₋₆ O,O′-alkylphosphoryl group in which thealkyl moiety may be substituted with a halogen atom, a cyano group, aformyl group or a nitro group. A C₁₋₆ alkylcarbonyl group in which thealkyl moiety may be substituted with a halogen atom, a C₁₋₆alkylsulfonyl group in which the alkyl moiety may be substituted with ahalogen atom, or a cyano group is preferred.

R₃ is a C₁₋₈ alkylene group which may be substituted with a halogenatom, a C₂₋₈ alkenylene group which may be substituted with a halogenatom, a C₂₋₈ alkynylene group which may be substituted with a halogenatom, a phenylene group which may be substituted, or a 5- or 6-memberedheterocyclic divalent group which may be substituted. A C₁₋₈ alkylenegroup which may be substituted with a halogen atom is preferred.

R₄ is a hydrogen atom, a cyano group, a phenyl group which may besubstituted, a 3- to 8-membered cyclic alkyl group which may besubstituted, a 3- to 8-membered heterocyclic which may be substituted, ahalogen atom, OR₅, OCOR₅, OCOOR₅, COR₅, COOR₅, SR₅, SOR₅, SO₂R₅,N—CO—OR₈, N—CO—SR₈, N—CS—OR₈, N—CS—SR₈, N—O—CO—R₈, O—CO—R₈, O—CO—OR₈,O—CO—SR₈, O—CS—OR₈, O—CS—SR₈, S—CS—OR₈, S—CS—SR₈, S—CO—OR₈, S—CO—SR₈,S—CS—R₈, NR₉R₁₀, O—CO—NR₉R₁₀, O—CS—NR₉R₁₀, S—CO—NR₉R₁₀ or S—CS—NR₉R₁₀.

Here, R₅ is a C₁₋₆ alkyl group which may be substituted with a halogenatom, an aryl group which may be substituted with a halogen atom or anaralkyl group which may be substituted with a halogen atom.

R₆ and R₇ are each independently a hydrogen atom or a C₁₋₆ alkyl groupwhich may be substituted with a halogen atom.

R₈ is a C₁₋₆ alkyl group which may be substituted, the substituent beinga halogen atom, a C₁₋₄ alkyloxycarbonyl group, a C₁₋₄ alkylcarbonylgroup, a benzoyl group which may be substituted with a halogen atom or aC₁₋₄ alkyl group which may be substituted with a halogen atom, a C₁₋₄alkyloxy group or a C₁₋₄ alkylthio group.

R₉ and R₁₀ are each independently a hydrogen atom, a formyl group, aC₁₋₆ alkyl group which may be substituted with a halogen atom, a C₁₋₆alkylcarbonyl group in which the alkyl moiety may be substituted with ahalogen atom, a C₁₋₆ alkylcarbonyloxy group in which the alkyl moietymay be substituted with a halogen atom, a phenyl group which may besubstituted (the substituent being a halogen atom, a C₁₋₄ alkyl groupwhich may be substituted with a halogen atom, or a C₁₋₄ alkyloxy groupwhich may be substituted with a halogen atom), or a benzyl group whichmay be substituted (the substituent being a halogen, a C₁₋₄ alkyl groupwhich may be substituted with a halogen or a C₁₋₄ alkyloxy group whichmay be substituted with a halogen), R⁹ and R¹⁰ together form a ring anddenote a 3- to 10-membered heterocycloalkyl group containing at leastone nitrogen atom, or N, R₉ and R₁₀ together form a ring and denote a 5-or 6-membered aromatic heterocycle containing at least one nitrogenatom.

The “C₁₋₆ alkyl group which may be substituted with a halogen atom” thatis represented by R₅, R₆, R₇, R₈, R₉ and R₁₀ is an alkyl group havingfrom 1 to 6 carbons that is linear, branched, cyclic or a combinationthereof. The upper limit in the number of halogen atoms which may besubstituted is the number of hydrogen atoms on the alkyl group. When abranched or cyclic alkyl group is included, it is apparent that thenumber of carbons is at least 3.

Illustrative examples of the “C₁₋₆ alkyl group which may be substitutedwith a halogen atom” that is represented by R₅ include a methyl group,an ethyl group, an n-propyl group, a difluoromethyl group, atrifluoromethyl group, a chloromethyl group and a 2-trifluoroethylgroup.

Illustrative examples of the “C₁₋₆ alkyl group which may be substitutedwith a halogen atom” that is represented by R₆ and R₇ include a methylgroup, an ethyl group, an n-propyl group, a difluoromethyl group, atrifluoromethyl group, a chloromethyl group and a 2-trifluoroethylgroup.

Illustrative examples of the “C₁₋₆ alkyl group which may be substitutedwith a halogen atom” that is represented by R₈ include a methyl group,an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group,an n-pentyl group, a 2-trifluoroethyl group and a 2-chloroethyl group. Amethyl group, an ethyl group, an n-propyl group, an isopropyl group, ann-butyl group or an n-pentyl group is preferred.

Illustrative examples of the “C₁₋₆ alkyl group which may be substitutedwith a halogen atom” that is represented by R₉ and R₁₀ include a methylgroup, an ethyl group, an n-propyl group, an isopropyl group, an n-butylgroup, an n-pentyl group, a 2-trifluoroethyl group and a 2-chloroethylgroup. A methyl group or an ethyl group is preferred.

The alkyl moiety in the “C₁₋₆ alkylcarbonyl group in which the alkylmoiety may be substituted with a halogen atom” that is represented byR₂, R₉ and R₁₀, the “C₁₋₆ alkyloxycarbonyl group in which the alkylmoiety may be substituted with a halogen atom,” the “C₁₋₆ alkylsulfonylgroup in which the alkyl moiety may be substituted with a halogen atom”and the “C₁₋₆ O,O′-alkylphosphoryl group in which the alkyl moiety maybe substituted with a halogen atom” that are represented by R₂, and the“C₁₋₆ alkylcarbonyloxy group in which the alkyl moiety may besubstituted with a halogen atom” that is represented by R₉ and R₁₀ is analkyl group having from 1 to 6 carbons that is linear, branched, cyclicor a combination thereof. The upper limit in the number of halogen atomswhich may be substituted is the number of hydrogen atoms on the alkylgroup. When a branched or cyclic alkyl group is included, it is apparentthat the number of carbons is at least 3.

Illustrative examples of the “C₁₋₆ alkylcarbonyl group in which thealkyl moiety may be substituted with a halogen atom” that is representedby R₂ include an acetyl group, an ethylcarbonyl group, ann-propylcarbonyl group, a difluoroacetyl group, a trifluoroacetyl group,a pentafluoroacetyl group, a chloroacetyl group and a trichloroacetylgroup. A trifluoroacetyl group is preferred.

Illustrative examples of the “C₁₋₆ alkyloxycarbonyl group in which thealkyl moiety may be substituted with a halogen atom” that is representedby R₂ include a methyloxycarbonyl group, an ethyloxycarbonyl group, ann-propyloxycarbonyl group, a chloromethyloxycarbonyl group and a2-trifluoroethyloxycarbonyl group.

Illustrative examples of the “C₁₋₆ alkylsulfonyl group in which thealkyl moiety may be substituted with a halogen atom” that is representedby R₂ include a methylsulfonyl group, an ethylsulfonyl group, ann-propylsulfonyl group, a difluoromethylsulfonyl group, atrifluoromethylsulfonyl group, a trichloromethylsulfonyl group and a2-trifluoromethylsulfonyl group. A trifluoromethylsulfonyl group ispreferred.

Illustrative examples of the “C₁₋₆ O,O′-alkylphosphoryl group in whichthe alkyl moiety may be substituted with a halogen atom” that isrepresented by R₂ include an O,O′-dimethylphosphoryl group and anO,O′-diethylphosphoryl group.

Illustrative examples of the “C₁₋₆ alkylcarbonyl group in which thealkyl moiety may be substituted with a halogen atom” that is representedby R₅ include an acetyl group, an ethylcarbonyl group, ann-propylcarbonyl group, an isopropylcarbonyl group and a2-chloroethylcarbonyl group.

Illustrative examples of the “C₁₋₆ alkylcarbonyl group in which thealkyl moiety may be substituted with a halogen atom” that is representedby R₉ and R₁₀ include a methyloxycarbonyl group, an ethyloxycarbonylgroup, an n-propyloxycarbonyl group, an isopropyloxycarbonyl group and a2-chloroethyloxycarbonyl group.

Illustrative examples of the “C₁₋₆ alkylcarbonyloxy group in which thealkyl moiety may be substituted with a halogen atom” that is representedby R₉ and R₁₀ include a methylcarbonyloxy group, an ethylcarbonyloxygroup, an n-propylcarbonyloxy group, an isopropylcarbonyloxy group and a2-chloroethylcarbonyloxy group.

The “C₁₋₈ alkylene group which may be substituted with a halogen atom”that is represented by R₃ is an alkylene group having from 1 to 8carbons that is linear, branched, cyclic or a combination thereof. Theupper limit in the number of halogen atoms which may be substituted isthe number of hydrogen atoms on the alkyl group. When a branched orcyclic alkyl group is included, it is apparent that the number ofcarbons is at least 3. Illustrative examples include a methylene group,an ethylene group, a propylene group, a butylene group, afluoromethylene group, a 1-chloroethylene group, a 2-methylethylenegroup, a cyclopropylene group, a 2-cyclopropylethylene group and a1,3-cyclopentylene group. A methylene group, an ethylene group or apropylene group is preferred. An ethylene group is more preferred.

The “C₂₋₈ alkenylene group which may be substituted with a halogen atom”that is represented by R₃ is an alkenylene group having from 2 to 8carbons that is linear, branched, cyclic or a combination thereof. Theupper limit in the number of halogen atoms which may be substituted isthe number of hydrogen atoms on the alkyl group. When a branched orcyclic alkyl group is included, it is apparent that the number ofcarbons is at least 3. Illustrative examples include a vinylene group, a1-propenylene group, a 2-fluoro-1-propenylene group, a2-methyl-1-propenylene group and a 2-cyclohexen-1,4-ylene group.

The “C₂₋₈ alkynylene group which may be substituted with a halogen atom”that is represented by R₃ is an alkynylene group having from 2 to 8carbons that is linear, branched, cyclic or a combination thereof. Theupper limit in the number of halogen atoms which may be substituted isthe number of hydrogen atoms on the alkyl group. When a branched orcyclic alkyl group is included, it is apparent that the number ofcarbons is at least 3. Illustrative examples include a propynylene groupand a butynylene group. 1-Propynylene is preferred.

The “phenylene which may be substituted” that is represented by R₃ is adivalent group from which two of the hydrogen atoms on benzene have beenremoved, and wherein the substituents are exemplified by halogen atoms,C₁₋₄ alkyl groups which may be substituted with a halogen atom, alkyloxygroups which may be substituted with a halogen atom, hydroxyl groups,cyano groups and nitro groups. Illustrative examples include a phenylenegroup, a 4-fluorophenylene group and a 2-methylphenylene group.

The “5- or 6-membered heterocyclic divalent group which may besubstituted” that is represented by R₃ is a divalent group from whichtwo of the hydrogen atoms on the 5- or 6-membered heterocycle have beenremoved, and wherein the substituents are exemplified by halogen atoms,C₁₋₄ alkyl groups which may be substituted with a halogen atom, alkyloxygroups which may be substituted with a halogen atom, hydroxyl groups,cyano groups and nitro groups. Illustrative examples include a2-pyridinylene group.

Substituents which may substituted in the “pyridyl group which may besubstituted” or the “pyrimidyl group which may be substituted” that isrepresented by Ar′ in the compound of the formula (Ie′) are exemplifiedby halogen atoms, C₁₋₄ alkyl groups which may be substituted with ahalogen atom, alkyloxy groups which may be substituted with a halogenatom, hydroxyl groups, cyano groups and nitro groups. Halogen atoms arepreferred.

Preferred examples of Ar in the compound of the formula (Ie) and of Ar′in the compound of the formula (Ie′) include a 3-pyridyl group, a6-chloro-3-pyridyl group, a 5-chloro-3-thiazolyl group, a6-chloro-5-fluoro-3-pyridyl group, a 6-bromo-3-pyridyl group, a6-fluoro-3-pyridyl group, a 5,6-dichloro-3-pyridyl group, a6-trifluoromethyl-3-pyridyl group and a 2-chloro-5-pyrimidyl group. A6-chloro-3-pyridyl group, a 6-fluoro-3-pyridyl group, a6-chloro-5-fluoro-3-pyridyl group, a 6-bromo-3-pyridyl group or a2-chloro-5-pyrimidyl group is more preferred.

Y in the compounds of formulas (Ie) and (Ie′) represents from 1 to 3substituents which may be the same or different.

The “C₁₋₆ alkyl group which may be substituted with a halogen atom”represented by Y in the compounds of formulas (Ie) and (Ie′) is an alkylgroup having from 1 to 6 carbons that is linear, branched, cyclic or acombination thereof. The upper limit in the number of halogen atomswhich may be substituted is the number of hydrogen atoms on the alkylgroup. When a branched or cyclic alkyl group is included, it is apparentthat the number of carbons is at least 3.

Illustrative examples include a methyl group, an ethyl group, a n-propylgroup, an isopropyl group, a n-butyl group, a t-butyl group, atrifluoromethyl group and a 2-chloroethyl group. A methyl group ispreferred.

Illustrative examples of the “C₁₋₆ alkyloxy group which may besubstituted with a halogen” represented by Y include a methoxy group, anethoxy group, a trifluomethyl group and a difluoromethyl group.

Preferred examples of Y are a hydrogen atom and halogens. A hydrogenatom is more preferred.

The “C₁₋₆ alkyl group substituted with a halogen atom” represented byR_(4e) in the compounds of formulas (Ie) and (Ie′) is an alkyl grouphaving from 1 to 6 carbons that is linear, branched, cyclic or acombination thereof. The upper limit in the number of halogen atomswhich are substituted is the number of hydrogen atoms on the alkylgroup. When a branched or cyclic alkyl group is included, it is apparentthat the number of carbons is at least 3.

Illustrative examples include a trifluoromethyl group, a trichloromethylgroup, a difluorochloromethyl group, a difluoromethyl group, adichloromethyl group, a dibromomethyl group, a chloromethyl group, adifluoroethyl group, a dichloroethyl group, a 2,2,2-trifluoroethylgroup, a pentafluoroethyl group and a difluorocyclopropyl group. Atrifluoromethyl group, a trichloromethyl group, a dichloromethyl group,a difluoromethyl group, a difluorochloromethyl group, a chloromethylgroup or a pentafluoroethyl group is preferred. A trifluoromethyl group,a difluoromethyl group, a difluorochloromethyl group, a chloromethylgroup or a pentafluoroethyl group is more preferred.

Illustrative examples of the “C₁₋₆ alkyloxy group which may besubstituted with a halogen” represented by R_(4e) include a methoxygroup, an ethoxy group, an isopropyloxy group and a trifluoromethoxygroup.

Preferred examples of R_(4e) are C₁₋₆ alkyl groups which may besubstituted with a halogen. A trifluoromethyl group, a difluoromethylgroup, a difluorochloromethyl group, a chloromethyl group or apentafluoroethyl group is more preferred.

Salts of the amine derivatives of chemical formula (I) which act as theactive ingredient in the pest control agent provided by the inventionare acid addition salts allowable in agricultural and livestockchemicals. Illustrative examples include hydrochlorides, nitrates,sulfates, phosphates and acetates.

In a preferred form of the compound of formula (I),

Ar is a 4-nitrophenyl group, a 4-cyanophenyl group, a 3,5-dibromophenylgroup, a 2,4-dibromophenyl group, a 6-chloro-3-pyridyl group, a5-chloro-3-thiazolyl group, a 6-chloro-5-fluoro-3-pyridyl group, a6-bromo-3-pyridyl group, a 6-fluoro-3-pyridyl group, a5,6-dichloro-3-pyridyl group or a 6-trifluoromethyl-3-pyridyl group;

R₁ is a hydrogen atom or a methyl group;

R₂ is a C₁₋₆ alkylcarbonyl group in which the alkyl moiety may besubstituted with a halogen atom, a C₁₋₈ alkylsulfonyl group in which thealkyl moiety may be substituted with a halogen atom, or a cyano group;

R₃ is a methylene group, an ethylene group, a propylene group or a1-propynylene group; and

R₄ is a hydrogen atom, a cyano group, SR₅ (R₅ being a C₁₋₆ alkyl groupwhich may be substituted with a halogen), S—CS—OR₈ or S—CS—SR₈ (R₈ beinga C₁₋₆ alkyl group which may be substituted with a halogen).

Preferred compounds are exemplified by the compounds of (i) to (iii)below.

(i) Compounds Wherein:

Ar is a 4-cyanophenyl group, a 4-nitrophenyl group, a 3,5-dichlorophenylgroup, a 3,5-dibromophenyl group, a 2,4-dibromophenyl group, a4-bromophenyl group, a 3-nitro-5-bromophenyl group, a 6-chloro-3-pyridylgroup, a 5-chloro-3-thiazolyl group, a 6-chloro-5-fluoro-3-pyridyl groupor a 6-trifluoromethyl-3-pyridyl group;

R₁ is a hydrogen atom;

R₂ is a trifluoromethylsulfonyl group;

R₃ is a methylene group, an ethylene group or a 1 propynylene group; and

R₄ is a hydrogen atom or a cyano group.

(ii) Compounds Wherein:

Ar is a 6-chloro-3-pyridyl group, a 5-chloro-3-thiazolyl group or a6-trifluoromethyl-3-pyridyl group;

R₁ is a hydrogen atom or a methyl group;

R₂ is a cyano group or a trifluoromethylcarbonyl group;

R₃ is an ethylene group; and

R₄ is a hydrogen atom, SR₅ (R₅ being a C₁₋₆ alkyl group which may besubstituted with a halogen), S—CS—OR₈ or S—CS—SR₈ (R₈ being a C₁₋₆ alkylgroup which may be substituted with a halogen).

(iii) Compounds of the Formula (Ie).

Especially preferred compounds are exemplified by the compounds of (i)to (iii) below.

(i) Compounds Wherein:

Ar is a 4-cyanophenyl group, a 4-nitrophenyl group, a 3,5-dichlorophenylgroup, a 3,5-dibromophenyl group, a 2,4-dibromophenyl group, a4-bromophenyl group, a 3-nitro-5-bromophenyl group, a 6-chloro-3-pyridylgroup, a 5-chloro-3-thiazolyl group, a 6-chloro-5-fluoro-3-pyridyl groupor a 6-trifluoromethyl-3-pyridyl group;

R₁ is a hydrogen atom;

R₂ is a trifluoromethylsulfonyl group;

R₃ is a methylene group, an ethylene group or a 1 propynylene group; and

R₄ is a hydrogen atom.

(ii) Compounds Wherein:

Ar is a 6-chloro-3-pyridyl group, a 5-chloro-3-thiazolyl group or a6-trifluoromethyl-3-pyridyl group;

R₁ is a hydrogen atom or a methyl group;

R₂ is a cyano group or a trifluoromethylcarbonyl group;

R₃ is an ethylene group; and

R₄ is SR₅ (R₅ being a C₁₋₆ alkyl group which may be substituted with ahalogen), S—CS—OR₈ or S—CS—SR₈ (R₈ being a C₁₋₆ alkyl group which may besubstituted with a halogen).

(iii) Compounds of the Formula (Ie).

Preferred forms of the compound of formula (Ie) are compounds wherein:

Ar is a 3-pyridyl group, a 6-chloro-3-pyridyl group, a5-chloro-3-thiazolyl group, a 6-chloro-5-fluoro-3-pyridyl group, a6-bromo-3-pyridyl group, a 6-fluoro-3-pyridyl group, a5,6-dichloro-3-pyridyl group, a 6-trifluoromethyl-3-pyridyl group or a2-chloro-5-pyrimidyl group;

R₁ is a hydrogen atom, a methyl group or an ethyl group;

Y is a hydrogen atom, a halogen atom or a methyl group; and

R_(4e) is a trifluoromethyl group, a trichloromethyl group, adichloromethyl group, a difluoromethyl group, a difluorochloromethylgroup, a chloromethyl group or a pentafluoroethyl group.

Compounds Wherein:

Ar is a 6-chloro-3-pyridyl group, a 6-fluoro-3-pyridyl group, a6-chloro-5-fluoro-3-pyridyl group, a 6-bromo-3-pyridyl group or a2-chloro-5-pyrimidyl group;

R₁ is a hydrogen atom or a methyl group;

Y is a hydrogen atom; and

R_(4e) is a trifluoromethyl group, a difluoromethyl group, adifluorochloromethyl group, a chloromethyl group or a pentafluoroethylgroup are more preferred.

The compound of chemical formula (I) which serves as the activeingredient of the pest control agent of the invention is preferably acompound which has a control activity (e.g., an insect mortality orknockdown rate of at least 30%, at least 50%, at least 80%, or 100%) infoliar application at 500 ppm, soil drenching treatment at 0.1mg/seedling, or local application at 2 μg/insect (see the test examplesfor the invention). Alternatively, the compound is one having a controlactivity (insecticidal effect), as determined by the evaluation ofinsect mobility, under the root immersion treatment at 20 μg/seedlingdescribed in Test Example 15 or under the culturing conditions at about3 ppm described in Test Example 21.

In foliar application, the compound is more preferably one having acontrol activity at a concentration of below 500 ppm (e.g., 400 ppm, 300ppm, 200 ppm, 100 ppm, 50 ppm, 30 ppm, 10 ppm, 5 ppm, 3 ppm, 1.5 ppm,1.25 ppm, 1 ppm, or 0.5 ppm)

In soil drenching treatment, the compound is more preferably one havinga control activity at a concentration below 0.1 mg/seedling (e.g., 0.05mg/seedling, 0.01 mg/seedling, 0.005 mg/seedling, or 0.002 mg/seedling).

In local application, the compound is more preferably one having acontrol activity at a concentration below 2 μg/insect (e.g., 1μg/insect, 0.5 μg/insect, or 0.2 μg/insect).

In dry film application, the compound is more preferably one having acontrol activity at a concentration below 200 ppm (e.g., 100 ppm, 50ppm, 30 ppm, or 10 ppm).

In root immersion treatment, the compound is more preferably one havinga control activity at a concentration below 20 μg/seedling (e.g., 10μg/seedling, 5 μg/seedling, 2 μg/seedling, 1 μg/seedling, 0.5μg/seedling, 0.1 μg/seedling, 0.05 μg/seedling, 0.03 μg/seedling, or0.01 μg/seedling).

Illustrative examples of the compounds of the invention are listed inTables 1 to 5.

TABLE 1 Compound No. Ar R₁ R₂ R₃ R₄ 1 (I) H CN CH₂CH₂ SCH₃ 2 (I) H CNCH₂CH₂ SCH₂CH₃ 3 (I) H CN CH₂CH₂ SCH₂CH₂CH₃ 4 (I) H CN CH₂CH₂CH₂ H 5 (I)H CN CH₂CH₂CH₂ SCH₃ 6 (I) H CN CH₂CH₂ SCSSCH₃ 7 (I) H CN CH₂CH₂SCSSCH₂CH₃ 8 (I) H CN CH₂CH₂ SCSSCH₂CH₂CH₃ 9 (II) H CN CH₂CH₂ SCSSCH₂CH₃10 (II) H CN CH₂CH₂ SCSSCH₂CH₂CH₃ 11 (I) H CN CH₂CH₂ OCH₃ 12 (I) H CNCH₂CH₂CH₂CH₂ H 13 (I) H CN CH₂ H 14 (I) H CN CH₂CH₂ H 15 (I) H CNCH(CH₃)CH₂ H 16 (I) H CN CH₂CH₂ N(CH₃)₂ 17 (I) H CN CH₂ (I) 18 (I) Me CNCH₂CH₂ H 19 (II) H CN CH₂CH₂ H 20 (I) H COMe CH₂CH₂ H 21 (I) H COCF₃CH₂CH₂ H 22 (I) H COOMe CH₂CH₂ H 23 (II) H CN CH₂CH₂ SCH₃ 24 (I) H COMeCH₂CH₂ SCH₃ 25 (I) H COOPh CH₂CH₂ SCH₃ 26 (I) H SOOPh CH₂CH₂ SCH₃ 27 (I)H COOMe CH₂CH₂ SCH₃ 28 (I) H SOOMe CH₂CH₂ SCH₃ 29 (I) H CHO CH₂CH₂ SCH₃30 (I) H COPh CH₂CH₂ SCH₃ 31 (I) H COCF₃ CH₂CH₂ SCH₃ 32 (II) H CN CH₂CH₂SCH₂CH₃ 33 (I) H PO(OC₂H₅)₂ CH₂CH₂ SCH₃ 34 (I) H COCCl₃ CH₂CH₂ SCH₃ 35phenyl H CN CH₂CH₂ H 36 3-pyridyl H CN CH₂CH₂ H 37 4-chlorophenyl H CNCH₂CH₂ H 38 phenyl H CN CH₂ phenyl 39 phenyl H COMe CH₂CH₂ H 40 phenyl HCOOMe CH₂CH₂ H 41 3-thienyl H CN CH₂CH₂ H 42 (I) H CN CH₂C≡C H 43 (I) HCN CH₂CH═CH H 44 (I) H CN CH₂ phenyl 45 3-cyanophenyl H CN CH₂CH₂ H 466-trifluoromethyl- H CN CH₂CH₂ H 3-pyridyl 47 6-trifluoromethyl- H CNCH₂CH₂ SCH₃ 3-pyridyl 48 6-trifluoromethyl- H CN CH₂CH₂ SCH₂CH₃3-pyridyl 49 (I) H CN CH₂CH₂ S-CH₂-(2- furanyl) 50 (I) H CN CH₂CH₂S-CH₂-phenyl 51 (I) H CN CH₂CH₂ SOO-phenyl 52 (I) H CN CH₂CH₂ S-phenyl53 (I) H CN CH₂CH₂ O-phenyl 54 (I) H CN CH₂CH₂ NHCOCH₃ 55 4-chlorophenylH CN CH₂ 4-chlorophenyl 56 (I) H CN CH₂ COOMe 57 (I) H CN CH₂CH₂ phenyl58 (I) H CN CH₂CH₂ COO-phenyl 59 (I) H CN CH₂ CN 60 (I) H CN CH(Me) CN

TABLE 2 Compound No. Ar R₁ R₂ R₃ R₄ 61 (I) H CN CH₂CH₂ OCOMe 62 (I) H CNCH₂ SCH₃ 63 (II) H CN CH₂CH₂ OCOMe 64 (II) H CN CH₂ SCH₃ 65 (II) H CNCH₂CH₂ COOMe 66 (II) H CN CH₂ cyclopropyl 67 (II) H CN CH(Me)CH SCH₃ 68(I) H CN 2-thiiranylene H 69 (I) H CN 2-oxyranylen H 70 (I) H CN CH₂CH₂COOMe 71 (I) H CN CH₂ cyclopropyl 72 5,6-dichloro- H CN CH₂CH₂ SCH₃3-pyridyl 73 (I) Me CN CH₂CH₂ SCH₃ 74 (II) H CN CH₂CH₂ SCH₃ 75 (II) H CNCH₂CH₂ SCH₂CH₃ 76 (I) H CN 3- H tetrahydrothiophenylene 77 (I) H CNCH(Me)CH SCH₃ 78 6-fluoro-3- H CN CH₂CH₂ SCH₃ pyridyl 79 6-chloro-5- HCN CH₂CH₂ SCH₃ fluoro-3- pyridyl 80 6-chloro-5- H CN CH₂CH₂ H fluoro-3-pyridyl 81 (I) H COCF₃ CH₂CHF H 82 (I) H CN CH₂CHF H 83 (I) H CN CH₂(II) 84 (I) H CN CH₂CH₂ OTs 85 (I) H CN CH₂CH₂ SCSN(Et)CH₂Ph 86 (I) H CNCH₂CH₂ SCSOEt 87 (II) H CN CH₂CH₂ SCSOEt 88 (I) H CN CH₂CH₂SCSN(Me)CH₂Ph 89 (I) Me COCF₃ CH₂CHF H 90 (I) H CN CH₂CH₂ SCSOiPr 91 (I)H CN CH₂CH₂ SCSO-n- pentyl 92 (I) Me CN CH₂CHF H 93 (I) H CN CH₂CH₂SCSO-n-Pr 94 (I) H CN CH₂CH₂ SCSO-n-Bu 95 (II) H CN CH₂CF₂ H 96 (I) MeCOCF₃ CH₂CF₂ H 97 (I) H COCF₃ CH₂CF₂ H 98 (I) H COCF₂Cl CH₂CF₂ H 99 (I)H COCCl₃ CH₂CF₂ H 100 (I) H CN CH₂CH₂CH₂ OTs 101 (I) H CN CH₂CH₂CH₂SCSOEt 102 (I) H CN CH₂CH₂CH₂ SCSO-n-Pr 103 (I) H CN CH₂CH₂CH₂SCSN(Et)CH₂Ph 104 (I) H SO₂CF₃ CH₂CF₂ H 105 (I) Me COCF₃ CH₂CH₂ H 106(I) Me COCF₃ CH₂CH₂CF₂ H 107 (I) Me SO₂CF₃ CH₂CH₂ H 108 (I) Me SO₂CF₃CH₂CF₂ H 109 (I) Et COCF₃ CH₂CF₂ H 110 (I) Et SO₂CF₃ CH₂CF₂ H 111 (I) EtCOCF₃ CH₂CH₂ H 112 (I) Et SO₂CF₃ CH₂CH₂ H 113 (I) H CN CH₂CH₂ S-CH₂-(2-imidazolyl) 114 6- Me SO₂CF₃ CH₂CH₂ H trifluoromethyl- 3-pyridyl 115 6-Me COCF₃ CH₂CH₂ H trifluoromethyl- 3-pyridyl 116 (II) Me SO₂CF₃ CH₂CH₂ H117 (II) Me SO₂CF₃ CH₂CF₂ H 118 (II) Et COCF₃ CH₂CF₂ H 119 (II) H CNCH₂CH═CH H 120 (II) H CN CH₂C≡C H

TABLE 3 Compound No. Ar R₁ R₂ R₃ R₄ 121 (II) H CN CH₂ H 122 (II) H CNCH₂CH₂CH₂ H 123 (II) Et SO₂CF₃ CH₂CF₂ H 124 2-pyridyl Me SO₂CF₃ CH₂CH₂ H125 (II) Et SO₂CF₃ CH₂CF₂ H 126 (II) Et COCF₃ CH₂CH₂ H 127 (II) EtSO₂CF₃ CH₂CH₂ H 128 (I) H SO₂CF₃ CH₂C≡C H 129 (I) H SO₂CF₃ CH₂ CN 1304-trifluoromethyl- H COCF₃ CH₂CH₂ H 3-pyridyl 131 6-trifluoromethyl- HSO₂CF₃ CH₂CH₂ H 3-pyridyl 132 4-pyridyl Me COCF₃ CH₂CH₂ H 133 3-pyridylMe COCF₃ CH₂CH₂ H 134 2-pyridyl Me COCF₃ CH₂CH₂ H 135 (I) H SO₂CF₃ CH₂ H136 (II) H CN CH₂CH₂ OTs 137 (II) H CN CH₂CH₂ SCSOEt 138 (II) H CNCH₂CH₂ SCSN(CH₂Ph)Et 139 (I) H CN CH₂CH₂ S(═O)Ph 140 (I) H SO₂CF₃CH₂CH₂CH₂ H 141 (I) H SO₂CF₃ CH₂CH₂CH₂CH₂ H 142 (I) H SO₂CF₃ CH₂CH₂SOOPh 143 (I) H SO₂CF₃ CH₂CH₂ OPh 144 (I) H SO₂CF₃ CH₂CH₂ H 145 (I) HSO₂CF₃ CH₂CH₂CH₂ H 146 (I) H SO₂CF₃ CH₂CH═CH H 147 (I) H SO₂CF₃ CH₂ Ph148 4-fluoro-3-pyridyl H CN CH₂CH₂ H 149 4-bromo-3-pyridyl H CN CH₂CH₂ H150 (I) H SO₂CF₃ CH₂CH₂ NMe₂ 151 (I) Me SO₂CF₃ CH₂CH₂ NMe₂ 152 (I) HSO₂CF₃ CH₂CH₂C≡C H 153 3-chloro-4-pyridyl H CN CH₂CH₂ H 1543-chloro-2-pyridyl H CN CH₂CH₂ H 155 (I) H SO₂CF₃ CH₂CH₂ OCH₃ 156 (II) HSO₂CF₃ CH₂CH₂ OCH₃ 157 6-chloro-3- H COCF₃ CH₂CH₂ H pyridazyl 1583,5-dichlorophenyl H CN CH₂CH₂ H 159 (I) H SO₂CF₃ CH₂CH₂ CN 160 (I) HSO₂CF₃ CH₂ COOMe 161 (I) H SO₂CF₃ CN₂ COOH 162 4-fluorophenyl H SO₂CF₃CH₂CH₂ OCH₃ 163 (II) H SO₂CF₃ CH₂ CN 164 4-methylphenyl H SO₂CF₃ CH₂CH₂OCH₃ 165 6-trifluoromethyl- H SO₂CF₃ CH₂ CN 3-pyridyl 166 2-pyridyl HSO₂CF₃ CH₂CH₂ OCH₃ 167 6-chloro-5-fluoro- H SO₂CF₃ CH₂ CN 3-pyridyl 1683-pyridyl H SO₂CF₃ CH₂CH₂ OCH₃ 169 4-pyridyl H SO₂CF₃ CH₂CH₂ OCH₃ 170(I) Me SO₂CF₃ CH₂ CN 171 (I) Me SO₂CF₃ CH₂C≡C H 172 (II) H SO₂CF₃ CH₂C≡CH 173 6-fluoro-3-pyridyl H SO₂CF₃ CH₂CH₂ OCH₃ 174 6-bromo-3-pyridyl HSO₂CF₃ CH₂CH₂ OCH₃ 175 3,5-dichlorophenyl Me COCF₃ CH₂CH₂ H 1763,5-dichlorophenyl H COCF₃ CH₂CH₂ H 177 phenyl H SO₂CF₃ CH₂CH₂ H 178 (I)H SO₂CH₂CF₃ CH₂CH₂ H 179 (I) H SO₂CH₂CF₃ CH₂C≡C H 180 3-chlorophenyl HSO₂CF₃ CH₂CH₂ H

TABLE 4 Compound No. Ar R₁ R₂ R₃ R₄ 181 4-chlorophenyl H SO₂CF₃ CH₂CH₂ H182 3-cyanophenyl H SO₂CF₃ CH₂CH₂ H 183 4-nitrophenyl H SO₂CF₃ CH₂CH₂ H184 3,5-dichlorophenyl H SO₂CF₃ CH₂C≡C H 185 4-methylphenyl H SO₂CF₃CH₂CH₂ H 186 4-cyanophenyl H SO₂CF₃ CH₂CH₂ H 187 4-methoxyphenyl HSO₂CF₃ CH₂CH₂ H 188 4-fluorophenyl H SO₂CF₃ CH₂CH₂ H 1893,5-dibromophenyl H SO₂CF₃ CH₂CH₂ H 190 4-bromophenyl H SO₂CF₃ CH₂CH₂ H191 3,5-dimethylphenyl H SO₂CF₃ CH₂CH₂ H 192 3-nitrophenyl H SO₂CF₃CH₂CH₂ H 193 2,4-dibromophenyl H SO₂CF₃ CH₂CH₂ H 1943-nitro-5-bromophenyl H SO₂CF₃ CH₂CH₂ H 195 3,5- H SO₂CF₃ CH₂CH₂ Hbistrifluoromethylphenyl 196 (I) H CN CH₂CH₂ SCSSCH₂COOCH₃ 197 (II) MeCN CH₂CH₂ SCSSCH₂CH₂CH₃ 198 (I) H CN CH₂CH₂ SCSSCH₂OMe 199 (I) H CNCH₂CH₂ SCSSCH₂SMe 200 (I) H CN CH₂CH₂ SCSSCH₂CO-(4- methylphenyl) 2013-tetrahydrofuranyl H CN CH₂CH₂ H 202 3-tetrahydrofuranyl H CN CH₂CH₂SMe 203 (I) H COPh CH₂CH₂ H 204 (I) H COCH₂CH₃ CF₂ H 205 (I) H CONH₂CH₂CH₂ H 206 (I) H CONHMe CH₂CH₂ H 207 (I) H CONMe₂ CH₂CH₂ H 208 (I) HNO₂ CH₂CH₂ H 209 (I) H COCClF₂ CH₂CH₂ H 210 (I) H CN phenylene H 211 (I)Me SO₂CF₃ CH₂ H 245 (I) H COMe CH₂ CN 246 (I) H COCF₃ CH₂ CN (I):6-chloro-3-pyridyl (II): 5-chloro-3-thiazolyl

TABLE 5 Compound No. Ar R₁ R_(4e) Y 212 (I) H CF₃ H 213 (II) H CF₃ H 214(I) H OCH₃ H 215 (I) H CF₃ 5-Cl 216 (I) H CF₃ 5-F 217 (I) H CF₃ 4-Cl 218(II) H CF₃ 5-Cl 219 (II) H CF₃ 5-F 220 (II) H CF₃ 4-Cl 221 (I) H CF₃3-Me 222 (I) H CF₃ 4-Me 223 (I) H CF₃ 5-Me 224 phenyl H CF₃ H 2254-chlorophenyl H CF₃ H 226 3-pyridyl H CF₃ H 2276-chloro-5-fluoro-3-pyridyl H CF₃ H 228 6-trifluoromethyl-3-pyridyl HCF₃ H 229 6-fluoro-3-pyridyl H CF₃ H 230 5,6-dichloro-3-pyridyl H CF₃ H231 6-bromo-3-pyridyl H CF₃ H 232 (I) H CF₃ 4-F 233 (I) H CF₃ 3-F 234(I) H CHCl₂ H 235 (I) H CCl₃ H 236 (I) H CH₂Cl H 237 (I) Me CF₃ H 238(I) H CHF₂ H 239 (I) H CF₂Cl H 240 (I) H CHClBr H 241 (I) H CHBr₂ H 242(I) H CF₂CF₃ H 243 2-chloro-pyrimidinyl H CF₃ H 244 (I) H CH₂Br H

The most preferred compounds are the following which appear in Table 5:

-   Compound No. 212:    N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamide,-   Compound No. 227:    N-[1-((6-chloro-5-fluoropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamide,-   Compound No. 229:    N-[1-((6-fluoropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamide,-   Compound No. 231:    N-[1-((6-bromopyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamide,-   Compound No. 237:    N-[1-(1-(6-chloropyridin-3-yl)ethyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamide,-   Compound No. 238:    N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2-difluoroacetamide,-   Compound No. 239:    2-chloro-N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2-difluoroacetamide,-   Compound No. 242:    N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,3,3,3-pentafluoropropanamide,    and-   Compound No. 243:    N-[1-((2-chloropyrimidin-5-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamide.

Compound No. 212 in Table 5,N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamide,has the following physical properties. These properties have not beenmentioned in any of the prior-art documents.

(a) In powder x-ray diffraction analysis, the compound has diffractionangle peaks at least at the following diffraction angles (20): 8.6±0.2°,14.2±0.2°, 17.5±0.2°, 18.3±0.2°, 19.7±0.2°, 22.3±0.2°, 30.9±0.2°,35.3±0.2°

(b) In differential scanning calorimetry (DSC), the compound exhibits amelting point of 155 to 158° C.

Examples of the types of pests on which pest control agents containingat least one of the inventive compounds of chemical formula (I) exhibitcontrol effects are given below.

Examples of agricultural/horticultural pests include lepidopterous pests(e.g., common cutworm, cabbage armyworm, armyworm, cabbage butterflycaterpillar, diamondback moth, beet armyworm, rice stem borer, grassleaf roller, rice green caterpillar, leaf roller moth, codling moth,leaf miner moth, oriental tussock moth, pests belonging to the genusAgrotis (Agrotis spp.), pests belonging to the genus Helicoverpa(Helicoverpa spp.), and pests belonging to the genus Heliothis(Heliothis spp.)), hemipterous pests (e.g., aphids (Aphididae,Adelgidae, Phylloxeridae) such as the green peach aphid, cotton aphid,Aphis fabae, corn leaf aphid, pen aphid, foxglove aphid, Aphiscraccivora, Macrosiphum euphorbiae, Macrosiphum avenae, Methopolophiumdirhodum, grain aphid, Schizaphis graminum, cabbage aphid, turnip aphid,spiraea aphid, rosy apple aphid, woolly apple aphid, Toxoptera aurantiiand brown citrus aphid; leafhoppers such as the green rice leafhopperand the tea green leafhopper; planthoppers such as the small brownplanthopper and the white-backed rice planthopper; stink bugs such asthe white-spotted bug, the southern green stink bug, the brown-wingedgreen bug and the rice leaf bug; whiteflies (Aleyrodidae) such as thesilverleaf whitefly, the sweet potato whitefly and the greenhousewhitefly; and scale insects such as Pseudococcus comstocki, the citrusmealybug, the white peach scale and the California red scale (e.g.,Diaspididae, Margarodidae, Ortheziidae, Aclerdiae, Dactylgpiidae,Kerridae, Pseudococcidae, Coccidae, Eriococcidae, Asterolecamidae,Beesonidae, Lecanodiaspididae, Cerococcidae)), coleopterous pests (e.g.,rice water weevil, adzuki bean weevil, yellow mealworm, Western cornroot worm, Southern corn root worm, cupreous chafer, soy bean beetle,striped flea beetle, cucurbit leaf beetle, Colorado potato beetle, riceleaf beetle, codling moth larvae and longicorn beetles), pests belongingto the order Acarina (e.g., the two-spotted spider mite, the Kanzawaspider mite and Panonychus citri), hymenopterous pests (e.g., sawflies),orthopterous pests (e.g., grasshoppers and locusts), dipterous pests(e.g., the housefly and leaf miner flies), thysanopterous pests (e.g.,melon thrips and Western flower thrips), and plant parasitic nematodes(the root knot nematode, the root lesion nematode, the rice white-tipnematode and the pine wood nematode).

Examples of animal parasitic pests include hard-bodied ticks (e.g., lonestar tick, Gulf Coast tick, cattle tick, Rocky Mountain wood tick, WestCoast tick, American dog tick, Haemaphysalis campanulata, Haemaphysalisflava, Haemaphysalis longicornis, Haemaphysalis megaspinosa, Ixodesnipponensis, Ixodes ovatus, Western black-legged tick, Ixodespersulcatus, castor bean tick, black-legged tick, Ornithodoros moubataand brown dog tick), Cheyletidae spp. (e.g., Cheyletiella blackei andCheyletiella yasguri), demodex mites (e.g., Demodex canis and Demodexcati), Psoroptidae spp. (e.g., Psoroptes communis), mange mites (e.g.,Chorioptes bovis and Otodectes cynotis), Dermanyssidae spp. (e.g.,Ornithonyssus sylviarum), parasitoid mites, feather mites (e.g.,Menacanthus cornutus and Pterolichus obtusis), Trombiculidae spp. (e.g.,Helenicula miyagawai and Leptotrombidium akamusi), fleas, (e.g., the catflea, dog flea, sticktight flea, human flea and Oriental rat flea),chewing lice (e.g., dog louse, chicken louse), sucking lice (e.g., hoglouse, dog sucking louse, body louse, Pediculus humanus, pubic louse,common bed bug), muscid flies, warble flies, stable flies, horse flies,sand flies (e.g., biting sand fly), tsetse fly, tabanid flies, aedinemosquitoes (e.g., the Tiger mosquito and yellow fever mosquito),culicine mosquitoes (e.g., Culex pipiens pallens), anophelinemosquitoes, biting midges, buffalo gnats, assassin bugs, the pharaohant, nematodes (e.g., Strongyloididae, Ancylostomatoidea, Strongylida(e.g., Haemonchus contortus, Nippostrongylus brasiliensis),Trichostrongyloidea, Metastrongyloidea (e.g., Metastrongylus apr,Anriostrongylus cantonesis, Aelurostrongylus abstrusus), Oxyuroidea,Haterakoidea (e.g., Ascaridiidae galli), Ascaridoidea (e.g., Anisakissimplex, Ascaris lumbricoides suum, Parascaris equorum, Toxocara canis,Toxocara cati), Spirurida (e.g., Subuluroidea, Gnathostoma spinigerum,Physaloptea praeputialis, Ascarops strongylina, Draschia megastoma,Ascaria hamulosa, Dracunculus medinensis), Filaroidea (e.g., Dirofilariaimmitis, Wuchereria bancrofti, Onchocerca volvulus, Loa loa),Dioctophymatoidea, Trichinelloidea (e.g., Trichuris vulpis, Trichinellaspiralis)), Trematoda (e.g., Schistosoma japonicum, Fasciola spp.),Acanthocephala, Cestoda (e.g., Pseudophyllidea (e.g., Spirometraerinaceieuropaei), Cyclophyllidea (e.g., Dipylidium caninum)), andProtozoa.

Health pests, nuisance pests, stored grain pests, stored food pests andhousehold pests include mosquitoes (e.g., the Tiger mosquito and Culexpipiens pallens), cockroaches (e.g., the smoky-brown cockroach,Periplaneta fuliginosa, and the German cockroach), grain mites (e.g.,the common grain mite), flies (e.g., the house fly, Sarcophagidae spp.,sand flies, small fruit flies and Chironomidae spp.), buffalo gnats,biting midges, hymenopterous insects (e.g., ants such as Camponotusjaponicas and fire ants, and hornets such as the Japanese giant hornet),arthropods of the order Isopoda (e.g., the rough woodlouse, wharf roach,pill bug), hemipterous insects (e.g., common bed bug), arthropods of thesubphylum Myriapoda (e.g., centipedes, Chilopoda spp., millipedes),arthropods of the order Araneae (e.g., the huntsman spider),coleopterous insects (e.g., ground beetle), arthropods of the orderCollembola (e.g., Onychiurus folsomi), insects of the order Dermaptera(e.g., the giant earwig), insects of the order Orthoptera (e.g.,Stenopelmatidae spp.), insects of the order Coleoptera (e.g., adzukibean weevil, rice weevil, cadelle, rust-red flour beetle, white-markedspider beetle, deathwatch, bark beetles, dermestid beetles, Chlorophorusdiadema), insects of the order Lepidoptera (e.g., pyralid moths, clothesmoths), Hemipeplidae spp., insects of the order Isoptera (e.g., thehouse termite, western drywood termite, Odontotermes formosanus), andthe order Thysanura (e.g., oriental silverfish).

Of these, preferred examples of pests on which suitable use may be madeof the inventive pest control agent include lepidopterous pests,hemipterous pests, thysanopterous pests, dipterous pests, coleopterouspests, animal parasitic fleas and ticks, and canine heartworms (e.g., atleast one pest selected from the group consisting of diamondback moth,common cutworm, cotton aphid, green peach aphid, small brownplanthopper, brown rice planthopper, white-backed rice planthopper,green rice leafhopper, rice leaf bug, brown-winged green bug, westernflower thrips, rice leaf beetle, rice water weevil, house fly,Haemaphysalis longicornis and canine heartworm). Hemipterous pests,coleopteous pests and hard-bodied ticks are more preferred. Planthoppersand the green rice leafhopper are especially preferred.

Therefore, the pest control agents provided by the present invention areexemplified by insecticides for agricultural and horticultural use,control agents for internal animal parasites, control agents forexternal animal parasites, control agents for sanitary pests, controlagents for nuisance pests, control agents for stored grain/stored foodpests, and control agents for household pests. Insecticides foragricultural and horticultural use, control agents for internal animalparasites and control agents for external animal parasites arepreferred.

The pest control agents of the invention may be prepared using, asidefrom a compound of chemical formula (I), a carrier suitable for theintended method of use.

When the pest control agent of the invention is an agricultural pestcontrol agent, the active ingredient is generally mixed with a suitablesolid carrier, liquid carrier, gaseous carrier, surfactant, dispersantand other adjuvants, and the agent is furnished in any desired form,such as an emulsifiable concentrate, liquid formulation, suspensionconcentrate, wettable powder, flowable concentrate, dust, granules,tablets, oil solution, aerosol or smoking agent.

Illustrative examples of solid carriers include talc, bentonite, clay,kaolin, diatomaceous earth, vermiculite, white carbon and calciumcarbonate.

Illustrative examples of liquid carriers include alcohols such asmethanol, n-hexanol and ethylene glycol, ketones such as acetone, methylethyl ketone and cyclohexanone, aliphatic hydrocarbons such as n-hexaneand kerosene, aromatic hydrocarbons such as toluene, xylene and methylnaphthalene, ethers such as diethyl ether, dioxane and tetrahydrofuran,esters such as ethyl acetate, nitriles such as acetonitrile andisobutyronitrile, acid amides such as dimethylformamide anddimethylacetamide, vegetable oils such as soy oil and cottonseed oil,dimethylsulfoxide, and water.

Illustrative examples of gaseous carriers include liquid propane gas,air, nitrogen, carbon dioxide and dimethyl ether.

Surfactants and dispersants which may be used for the purpose ofemulsification, dispersion, spreading, sticking and the like includealkylsulfuric acid esters, alkyl(aryl)sulfonic acid salts,polyoxyalkylene alkyl(aryl)ethers, polyol esters, and ligninsulfonicacid salts.

Adjuvants which may be used for improving the properties of theformulation include carboxymethylcellulose, gum arabic, polyethyleneglycol and calcium stearate.

The above carriers, surfactants, dispersants and adjuvants may each beused singly or in combination, as needed.

The active ingredient content within the above formulation, although notparticularly limited, is typically set to from 1 to 75 wt % inemulsifiable concentrates, from 0.3 to 25 wt % in dusts, from 1 to 90 wt% in wettable powders, and from 0.5 to 10 wt % in granules.

The compounds of chemical formula (I), formulations containing thesecompounds, and mixtures of these with other pest control agents may besuitably applied to, for example, insect pests, plants, plantpropagation materials (e.g., seeds, plant foliage, roots, germinatedplants, and seedlings), soils, nutrient solutions in hydroponics, solidmedia in hydroponics, or rooms needed to prevent infestation by pests.Plants subjected to such application include genetically modified crops.

Such application may be carried out before and after pest infestation.

In particular, the compounds of chemical formula (Ie), formulationscontaining the same, and combinations of these with other pest controlagents, by being applied at an effective dose to a target selected fromthe group consisting of seeds, roots, tubers, bulbs, rhizomes,germinated plants, seedlings, soils, nutrient solutions in hydroponicsand solid media in hydroponics, and thus being allowed to penetrate andtranslocate into the plant, are able to control pests.

In cases where the above targets of application are the seeds, roots,tubers, bulbs or rhizomes of plants, preferred examples of the method ofapplication are not particularly limited provided penetration andtranslocation is unhindered and include, for example, dipping methods,dust coating methods, smearing methods, spraying methods, pellet methodsand film coating methods.

In the case of seeds, examples of the method of application includedipping, dust coating, smearing, spraying, pellet application, filmcoating and fumigation. Dipping is a method for immersing the seeds in aliquid solution of the pest control agent. Dust coating methods includedry dust coating which involves coating the pest control agent inpowdered form onto dry seeds, and wet dust coating which involvescoating the pest control agent in powdered form onto lightlywater-moistened seeds. Other methods are a smearing method for applyingthe pest control agent in a suspended form onto the surface of seedswithin a mixer, and a spraying method for spraying the same onto thesurface of the seeds. Additional methods of application include a pelletmethod in which, when the seeds are formed together with a filler intopellets of a given size and shape, treatment is carried out by mixingthe pest control agent with the filler; a film coating method whichentails coating the seeds with a film containing the pest control agent;and a fumigation method which entails disinfection of the seeds with thepest control agent that has been gasified within a closed vessel.

In the case of application to germinated plants and seedlings, theseplants may be protected by application, via systemic or partialtreatment by dipping, following germination and following emergence fromthe soil, but prior to transplantation.

In the case of application to seeds, roots, tubers, bulbs or rhizomes,an additional consideration is planting or dipping the seeds, roots,tubers, bulbs or rhizomes for a time sufficient to allow penetration andtranslocation of the pest control agent. In such a case, the time andtemperature at which dipping is carried out may be suitably determinedby a person skilled in the art in accordance with the target ofapplication and the type and dose of the chemical. In addition, thepenetration and translocation time is not subject to any particularlimitation, and may be, for example, 1 hour or more. The temperatureduring penetration and translocation is, for example, from 5 to 45° C.

Methods of application to the soil are exemplified by the application ofthe inventive compound, formulations containing the same, or granules ofmixtures thereof with other pest control agents, either into soil oronto soil. Preferred soil application methods are spraying, bandapplication, furrow application and planting hole treatment. Here,spraying treatment is surface treatment over the entire surface area tobe treated, and encompasses subsequent mechanical introduction into thesoil.

Another useful method of soil treatment involves application bydrenching soil with a solution of the inventive compounds, a formulationcontaining the same, or a mixture thereof with another pest controlagent that has been emulsified or dissolved in water.

In the case of application to nutrient solutions in nutriculturalsystems for the production of vegetables and flowering plants, such assolid medium cultivation, including hydroponics, sand culture, thenutrient film technique (NFT) and the rock wool technique, it is obviousthat the inventive compounds or formulations containing the same, ormixtures of these with other pest control agents, can be directlyapplied to an artificial plant growth medium containing vermiculite or asolid medium containing an artificial mat for raising seedlings.

In the above application step, the effective dose of the compound offormula (I) or a salt thereof, or of a compound of formula (Ie) or asalt thereof, is preferably an amount sufficient for the compound offormula (I) or formula (Ie) to penetrate and translocate in thesubsequent penetration and translocation step.

This effective dose may be suitably decided while taking intoconsideration such factors as the properties of the compound, the typeand amount of the target of application, the length of the subsequentpenetration and translocation step, and the temperature. For example, inthe case of application to seeds, the dose of the compound of formula(I) or a salt thereof, or of the compound of formula (Ie) or a saltthereof, is preferably from 1 g to 10 kg, and more preferably from 10 gto 1 kg, per 10 kg of seed. In the case of application to soil, the doseof the compound of formula (I) or a salt thereof, or of the compound offormula (Ie) or a salt thereof, is preferably from 0.1 g to 10 kg, andmore preferably from 1 g to 10 kg, per 10 ares of cultivated land. Inthe case of foliar application to plants, the dose of the compound offormula (I) or a salt thereof, or of the compound of formula (Ie) or asalt thereof, is preferably from 0.1 g to 10 kg, and more preferablyfrom 1 g to 1 kg, per 10 areas of cultivated land.

In cases where the pest control agent of the invention is an agent forcontrolling animal parasitic pests, it may be furnished as, for example,a liquid formulation, an emulsifiable concentrate, liquefied dropformulation, a spray, a foam formulation, tablets, granules, finegranules, a dust, capsules, tablets, a chewable preparation, aninjection, a suppository, a cream, a shampoo, a rinse, a resinformulation, a smoking agent or as poisonous bait. Supply as a liquidformulation or a liquid formulation for drop is especially preferred.

In liquid formulations, adjuvants such as common emulsifying agents,dispersants, spreaders, wetting agents, suspending agents preservativesand propellants may also be included, in addition to which ordinaryfilm-forming agents may be included as well. Surfactants which may beused for emulsification, dispersion, spreading, sticking and the likeinclude soaps, polyoxyalkylene alkyl(aryl)ethers, polyoxyethylenealkylallyl ethers, polyoxyethylene fatty acid esters, higher alcoholsand alkyl aryl sulfonates. Examples of dispersants include casein,gelatin, polysaccharides, lignin derivatives, sugars and syntheticwater-soluble polymers. Examples of spreading and wetting agents includeglycerol and polyethylene glycol. Examples of suspending agents includecasein, gelatin, hydroxypropyl cellulose and gum arabic. Examples ofstabilizers include phenol-based antioxidants (e.g., BHT, BHA),amine-based antioxidants (e.g., diphenylamine), and organosulfur-basedantioxidants. Examples of preservatives include methyl p-oxybenzoate,ethyl p-oxybenzoate, propyl p-oxybenzoate and butyl p-oxybenzoate. Theabove carriers, surfactants, dispersants and adjuvants may each be used,as needed, either singly or as combinations thereof. In addition,fragrances and synergists may also be included. In a liquid formulation,it is suitable for the active ingredient content in the pest controlagents of the invention to be generally from 1 to 75 wt %.

Carriers used for preparing a cream formulation are exemplified bynon-volatile hydrocarbons (e.g., liquid paraffin), lanolin fats addedwith water and oils, higher fatty acids, fatty acid esters, vegetableoils, silicone oils, and water. In addition, emulsifying agents,humectants, antioxidants, fragrances, borax and ultraviolet absorbersmay each be used, either singly or in combination thereof, as needed.Examples of emulsifying agents include fatty acid sorbitans,polyoxyethylene alkyl ethers and fatty acid polyoxyethylenes. An activeingredient content within the inventive pest control agent of generallyfrom 0.5 to 70 wt % is appropriate in cream formulations.

In the case of capsules, pills or tablets, the active ingredient withinthe inventive composition is suitably divided up and mixed with adiluting liquid or a carrier such as starch, lactose or talc, inaddition to which a disintegrant such as magnesium stearate and/or abinder are added. If necessary, the formulation may be tableted prior touse.

In the case of injections, preparation must be carried out as a sterilesolution. The injection may include sufficient salt or glucose to renderthe solution isotonic with blood. Examples of carriers that may be usedto prepare the injection include organic solvents such as glycerides,benzyl benzoate, isopropyl myristate, the fatty acid derivatives ofpropylene glycol and other esters, and N-methylpyrrolidone and glycerolformal. An active ingredient content within the inventive pest controlagent of generally from 0.01 to 10 wt % is appropriate in injections.

Examples of carriers for preparing a resin formulation include vinylchloride-based polymers and polyurethane. If necessary, a plasticizersuch as a phthalic acid ester, an adipic acid ester or stearic acid maybe added as the base for such formulations. After kneading the activeingredient into this base, the resin formulation is shaped such as byinjection molding, extrusion or molding under applied pressure. Inaddition, by suitably passing through such steps as molding and cutting,the formulation may be rendered into ear tags for animals and pestcontrol collars for animals.

Examples of carriers for poisoned bait include feed substances andattractants (e.g., cereal flours such as wheat flour and cornmeal,starches such as corn starch and potato starch, sugars such as granularsugar, barley malt and honey, flood flavors such as glycerol, onionflavor and milk flavor, animal-based powders such as silkworm powder andfish powder, and various pheromones). An active ingredient contentwithin the inventive pest control agent of generally from 0.0001 to 90wt % is appropriate in poisoned bait.

Pest control may be carried out by administering the inventive pestcontrol agent within the body of the target animal, either orally or byinjection, or by applying the inventive pest control agent to all orpart of the body surface of the target animal. Alternatively, pestcontrol may also be carried out by coating places where it is expectedthat pests will invade, parasitize or move through with the pest controlagent of the invention.

The pest control agent of the invention may be used directly as is, ormay, depending on the particular case, be applied after dilution with,for example, water, a liquid carrier, or a commercial shampoo, rinse,feed or animal bedding.

Also, the pest control agents according to the invention may be used inadmixture with other chemicals, such as fungicides, insecticides,acaricides, herbicides, plant growth regulators and fertilizers.Chemicals which may be used in admixture include compounds cited in thePesticide Manual (13^(th) edition, published by The British CropProtection Council) and the Shibuya Index (13^(th) edition, 2008,published by the Shibuya Index Research Group). Specific examples ofinsecticides, acaricides and nematicides include organophosphatecompounds such as acephate, dichlorvos, EPN, fenitothion, fenamifos,prothiofos, profenofos, pyraclofos, chlorpyrifos-methyl, diazinon,fosthiazate and imicyafos; carbamate compounds such as methomyl,thiodicarb, aldicarb, oxamyl, propoxur, carbaryl, fenobucarb,ethiofencarb, fenothiocarb, pirimicarb, carbofuran and benfuracarb;nereistoxin derivatives such as cartap and thiocyclam; organochlorinecompounds such as dicofol and tetradifon; pyrethroid compounds such aspermethrin, tefluthrin, cypermethrin, deltamethrin, cyhalothrin,fenvalerate, fluvalinate, ethofenprox and silafluofen; benzoyl ureacompounds such as diflubenzuron, teflubenzuron, flufenoxuron andchlorfluazuron; juvenile hormone-like compounds such as methoprene; andmolting hormone-like compounds such as chromafenozide. Examples of othercompounds include buprofezin, hexythiazox, amitraz, chlordimeform,pyridaben, fenpyroxymate, pyrimidifen, tebufenpyrad, tolfenpyrad,fluacrypyrim, acequinocyl, cyflumetofen, flubendizmide, ethiprole,fipronil, ethoxazle, imidacloprid, clothianidin, thiamethoxam,acetamiprid, nitenpyram, thiazcloprid, dinotefuran, pymetrozine,bifenazate, spirodiclofen, spiromesifen, flonicamid, chlorfenapyr,pyriproxyfen, indoxacarb, pyridalyl, spinosad, avermectin, milbemycin,cyneopyrafen, spinetoram, pyrifluquinazon, chlorantraniliprole,cyantraniliprole, spirotetramat, lepimectin, metafluminzone,pyrafluprole, pyriprole, hydramethylnon, triazamate, sulfoxaflor,flupyradifurone, flometoquin, organometallic compounds, dinitrocompounds, organosulfur compounds, urea compounds, triazine compoundsand hydrazine compounds.

The pest control agents of the invention may also be used in admixtureor concomitantly with microbial pesticides such as BT formulations andentomopathogenic virus formulations.

Examples of fungicides which may be used in admixture or concomitantlyinclude strobilurin compounds such as azoxystrobin, kresoxym-methyl,trifloxystrobin, metominostrobin and orysastrobin; anilinopyrimidinecompounds such as mepanipyrim, pyrimethanil and cyprodinil; azolecompounds such as triadimefon, bitertanol, triflumizole, metoconazole,propiconazole, penconazole, flusilazole, myclobutanil, cyproconazole,tebuconazole, hexaconazole, prochloraz and simeconazole; quinoxalinecompounds such as quinomethionate; dithiocarbamate compounds such asmaneb, zineb, mancozeb, polycarbamate and propineb; phenylcarbamatecompounds such as diethofencarb; organochlorine compounds such aschlorothalonil and quintozene; benzimidazole compounds such as benomyl,thiophanate-methyl and carbendazole; phenylamide compounds such asmetalaxyl, oxadixyl, ofurase, benalaxyl, furalaxyl and cyprofuram;sulfenic acid compounds such as dichlofluanid; copper compounds such ascopper hydroxide and oxine-copper; isoxazole compounds such ashydroxyisoxazole; organophosphorus compounds such as fosetyl-aluminiumand tolclofos-methyl; N-halogenothioalkyl compounds such as captan,captafol and folpet; dicarboxylmide compounds such as procymidone,iprodione and vinchlozolin; carboxyanilide compounds such as flutolanil,mepronil, furamepyr, thifluzamide, boscalid and penthiopyrad; morpholinecompounds such as fenpropimorph and dimethomorph; organotin compoundssuch as fenthin hydroxide and fenthin acetate; cyanopyrrole compoundssuch as fludioxonil and fenpiclonil; and also tricyclazole, pyroquilon,carpropamid, diclocymet, fenoxanil, fthalide, fluazinam, cymoxanil,triforine, pyrifenox, fenarimol, fenpropidin, pencycuron, ferimzone,cyazofamid, iprovalicarb, benthiavalicarb-isopropyl,iminoctadin-albesilate, cyflufenamid, kasugamycin, validamycin,streptomycin, oxolinic acid, tebufloquin, probenazole, tiadinil andisotianil.

Methods for Synthesizing the Compounds of the Invention

(1) Compounds of chemical formula (Ia) below

(wherein Ar is a phenyl group which may be substituted, or a 5- or6-membered heterocycle which may be substituted;

R₂ is a C₁₋₆ alkylcarbonyl group in which the alkyl moiety may besubstituted with a halogen atom, a C₁₋₆ alkyloxycarbonyl group in whichthe alkyl moiety may be substituted with a halogen atom, a C₁₋₆alkylsulfonyl group in which the alkyl moiety may be substituted with ahalogen atom, CONR₆R₇ (wherein R₆ and R₇ are each independently ahydrogen atom or a C₁₋₆ alkyl group which may be substituted with ahalogen), a C₁₋₆ O,O′-alkylphosphoryl group in which the alkyl moietymay be substituted with a halogen atom, a cyano group, a formyl group ora nitro group;

R₃ is a C₁₋₈ alkylene group which may be substituted with a halogenatom, a C₂₋₈ alkenylene group which may be substituted with a halogenatom, a C₂₋₈ alkynylene group which may be substituted with a halogenatom, a phenylene group which may be substituted, or a 5- or 6-memberedheterocyclic divalent group which may be substituted; and

R₄ is a hydrogen atom, a phenyl group which may be substituted, a 3- to8-membered carbocycle or heterocycle which may be substituted, a halogenatom, OR₅, OCOR₅, OCOOR₅, COR₅, COOR₅, SR₅, SOR₅, SO₂R₅ (wherein R₅ is aC₁₋₆ alkyl group, an aryl group or an aralkyl group, any of which may besubstituted with a halogen), N—CO—OR₈, N—CO—SR₈, N—CS—OR₈, N—CS—SR₈,N—O—CO—R₈, O—CO—R₈, O—CO—OR₈, O—CO—SR₈, O—CS—OR₈, O—CS—SR₈, S—CS—OR₈,S—CS—SR₈, S—CO—OR₈, S—CO—SR₈ (wherein R₈ is a C₁₋₆ alkyl group which maybe substituted, the substituent being a halogen, a C₁₋₄ alkyloxycarbonylgroup, a C₁₋₄ alkylcarbonyl group, a benzoyl group which may besubstituted with a halogen or a C₁₋₄ alkyl group which may besubstituted with a halogen, a C₁₋₄ alkyloxy group or a C₁₋₄ alkylthiogroup), or NR₉R₁₀ (wherein R₉ and R₁₀ are each independently a hydrogenatom, a C₁₋₆ alkyl group which may be substituted with a halogen, a C₁₋₆alkylcarbonyl group in which the alkyl moiety may be substituted with ahalogen atom, or a C₁₋₆ alkylcarbonyloxy group in which the alkyl moietymay be substituted with a halogen atom);

with the proviso that when Ar is a 2,6-dichloro-4-pyridyl group, R₂ isnot a C₁₋₆ alkyloxycarbonyl group in which the alkyl moiety may besubstituted with a halogen atom)

may be obtained by reacting, for example, a halide, anhydride or esterof R₂ (R₂ having the same meaning as defined in above chemical formula(I)) with a compound of the following chemical formula (II)

(wherein Ar, R₃ and R₄ have the same meanings as defined in abovechemical formula (I)), either in the presence or absence of a base.

Carboxylic acid halides, carboalkyloxy halides, sulfonyl halides,O,O′-alkylphosphoryl halides, carboxylic anhydrides,dialkyldicarbonates, carboxylic acid esters and carbonic acid esters maybe used as the halide, anhydride or ester of R₂. For example, the use ofacetyl chloride, ethyl chloroformate, methanesulfonyl chloride, diethylchlorophosphate, trifluoroacetic anhydride or ethyl formate ispreferred.

When the reaction is carried out in the presence of a base, the base maybe, for example, an alkali metal hydride such as sodium hydride, acarbonate such as potassium carbonate or sodium carbonate, an alkalimetal hydroxide such as potassium hydroxide or sodium hydroxide, atertiary amine such as triethylamine, or a substituted or unsubstitutedpyridine compound such as pyridine or 4-dimethylaminopyridine.

The reaction may be carried out in the absence of a solvent or using asolvent which does not affect the reaction. In cases where a solvent isused, solvents such as amides (e.g., dimethylformamide,dimethylacetamide), nitriles (e.g., acetonitrile), sulfoxides (e.g.,dimethylsulfoxide), ethers (e.g., diethyl ether, tetrahydrofuran),esters (e.g., ethyl acetate, butyl acetate), aromatic hydrocarbons(e.g., benzene, xylene, toluene), alcohols (e.g., methanol, ethanol,propanol), ketones (e.g., acetone, methyl ethyl ketone), aliphatichydrocarbons (e.g., hexane, heptane, octane), halogenated hydrocarbons(e.g., dichloromethane, chloroform, chlorobenzene, dichlorobenzene), orwater may be used singly or as combinations of two or more thereof. Theuse of dimethylformamide, acetonitrile, ethers, dichloromethane,chloroform or the like is preferred.

The reaction may generally be carried out at from −80 to 100° C., and ispreferably carried out in the range of 20 to 50° C.

When R₂ in the above chemical compound (Ia) is a C₁₋₆ alkylcarbonylgroup in which the alkyl moiety may be substituted with a halogen atom,the compound of formula (Ia) may be obtained by reacting the compound ofchemical formula (II) with a carboxylic acid of the formula R₂, —COOH(wherein R_(2′) is a alkyl group which may be substituted with a halogenatom) in the presence of a dehydration-condensation agent.

A carbodiimide compound such as dicyclohexylcarbodiimide or1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride may be usedas the dehydration-condensation agent.

The reaction is preferably carried out using a solvent. For example,amides such as dimethylformamide and dimethylacetamide, nitriles such asacetonitrile, sulfoxides such as dimethylsulfoxide, ethers such asdiethyl ether and tetrahydrofuran, esters such as ethyl acetate andbutyl acetate, aromatic hydrocarbons such as benzene, xylene andtoluene, ketones such as acetone and methyl ethyl ketone, aliphatichydrocarbons such as hexane, heptane and octane, and halogenatedhydrocarbons such as dichloromethane, chloroform, chlorobenzene anddichlorobenzene may be used singly or as combinations of two or morethereof. The use of, for example, dichloromethane or chloroform ispreferred.

The reaction may be carried out at generally from −80 to 100° C., and ispreferably carried out in the range of 20 to 50° C.

When R₂ in above chemical formula (Ia) is a cyano group, the compound offormula (Ia) may be obtained by reacting the compound of formula (II)with a known cyanating reagent, either in the presence or absence of abase.

Cyanating reagents that may be used for this purpose include cyanogenbromide, cyanogen iodide, 1-cyanoimidazole, 1-cyanobenzotriazole, andsubstituted or unsubstituted benzenesulfonyl cyanide.

When the reaction is carried out in the presence of a base, the base maybe, for example, an alkali metal hydride such as sodium hydride, acarbonate such as potassium carbonate or sodium carbonate, an alkalimetal acetate such as sodium acetate, a tertiary amine such astriethylamine, or a substituted or unsubstituted pyridine compound suchas pyridine or 4-dimethylaminopyridine.

The reaction may be carried out in the absence of a solvent or using asolvent which does not affect the reaction. In cases where a solvent isused, solvents such as amides (e.g., dimethylformamide,dimethylacetamide), nitriles (e.g., acetonitrile), sulfoxides (e.g.,dimethylsulfoxide), ethers (e.g., diethyl ether, tetrahydrofuran),esters (e.g., ethyl acetate, butyl acetate), aromatic hydrocarbons(e.g., benzene, xylene, toluene), alcohols (e.g., methanol, ethanol,propanol), ketones (e.g., acetone, methyl ethyl ketone), aliphatichydrocarbons (e.g., hexane, heptane, octane), halogenated hydrocarbons(e.g., dichloromethane, chloroform, chlorobenzene, dichlorobenzene), orwater may be used singly or as combinations of two or more thereof. Theuse of an ether such as diethyl ether or tetrahydrofuran, or ahalogenated hydrocarbon such as dichloromethane or chloroform ispreferred. The reaction may be carried out at generally from 0 to 100°C., although it is preferable to add the cyanating reagent at 0° C. andgradually raise the temperature to about 20 to 50° C.

The compound of chemical formula (II) may be synthesized from a compoundof chemical formula (IIIa) or chemical formula (IIIb) below:

(wherein X is a halogen, OTs or Oms)

(wherein Ar has the same meaning as defined in above chemical formula(I)).

When synthesis is carried out from the compound of formula (IIIa), thecompound of formula (II) may be obtained by reacting the compound offormula (IIIa) with a compound of the chemical formula (IVa) below

(wherein R₃ and R₄ have the same meanings as defined above in chemicalformula (I)), either in the presence or absence of a base.

When the reaction is carried in the presence of a base, the base usedfor this purpose may be, for example, an alkali metal hydride such assodium hydride, a carbonate such as potassium carbonate or sodiumcarbonate, an alkali metal hydroxide such as potassium hydroxide orsodium hydroxide, a tertiary amine such as triethylamine, or asubstituted or unsubstituted pyridine compound such as pyridine or4-dimethylaminopyridine.

The reaction may be carried out in the absence of a solvent or using asolvent which does not affect the reaction. In cases where a solvent isused, solvents such as amides (e.g., dimethylformamide,dimethylacetamide), nitriles (e.g., acetonitrile), sulfoxides (e.g.,dimethylsulfoxide), ethers (e.g., diethyl ether, tetrahydrofuran),esters (e.g., ethyl acetate, butyl acetate), aromatic hydrocarbons(e.g., benzene, xylene, toluene), alcohols (e.g., methanol, ethanol,propanol), ketones (e.g., acetone, methyl ethyl ketone), aliphatichydrocarbons (e.g., hexane, heptane, octane), or halogenatedhydrocarbons (e.g., dichloromethane, chloroform, chlorobenzene,dichlorobenzene) may be used singly or as combinations of two or morethereof. The use of dimethylformamide, acetonitrile, an ether,dichloromethane or chloroform is preferred.

The reaction may be carried out at generally from 0 to 200° C., althoughit is preferable to add the reagent at 0° C., gradually raise thetemperature to about 20 to 50° C., then let the temperature rise to ahigher temperature as the reaction proceeds.

The amount of the compound of formula (IIIa) added is preferably notmore than one mole per mole of the compound of formula (IVa).

In the case of synthesis from the compound of formula (IIIb), thecompound of formula (II) may be obtained by reacting a compound of thefollowing chemical formula (IVb) with the compound of formula (IIIb)

(wherein R₃ and R₄ have the same meanings as defined in above chemicalformula (I), and X is a halogen atom, OTs or OMs), either in thepresence or absence of a base.

When the reaction is carried in the presence of a base, the base may be,for example, an alkali metal hydride such as sodium hydride, a carbonatesuch as potassium carbonate or sodium carbonate, an alkali metalhydroxide such as potassium hydroxide or sodium hydroxide, a tertiaryamine such as triethylamine, or a substituted or unsubstituted pyridinecompound such as pyridine or 4-dimethylaminopyridine.

The reaction may be carried out in the absence of a solvent or using asolvent which does not affect the reaction. In cases where a solvent isused, solvents such as amides (e.g., dimethylformamide,dimethylacetamide), nitriles (e.g., acetonitrile), sulfoxides (e.g.,dimethylsulfoxide), ethers (e.g., diethyl ether, tetrahydrofuran),esters (e.g., ethyl acetate, butyl acetate), aromatic hydrocarbons(e.g., benzene, xylene, toluene), alcohols (e.g., methanol, ethanol,propanol), ketones (e.g., acetone, methyl ethyl ketone), aliphatichydrocarbons (e.g., hexane, heptane, octane), halogenated hydrocarbons(e.g., dichloromethane, chloroform, chlorobenzene, dichlorobenzene), orwater may be used singly or as combinations of two or more thereof. Theuse of dimethylformamide, acetonitrile, an ether, dichloromethane orchloroform is preferred.

The reaction may be carried out at generally from 0 to 200° C., althoughit is preferable to add the reagent at 0° C., gradually raise thetemperature to about 20 to 50° C., then let the temperature rise to ahigher temperature as the reaction proceeds.

The amount of the compound of formula (IVb) added is preferably not morethan one mole per mole of the compound of formula (IIIb).

Alternatively, the compound of formula (II) may be obtained by adding acompound of the formula (IVc) below, either in the presence or absenceof an acid, to the compound of formula (IIIb) so as to form an imine,then carrying out a reducing reaction.

(In the formula, R_(3′) and R_(3″) which may be the same or different,are each independently a hydrogen atom or a alkyl group, and R_(3′) andR_(3″) may together form a ring, with the provisos that R_(3′) andR_(3″) are not both hydrogen atoms and that the sum of the numbers ofcarbon atoms on R_(3′) and R_(3″) is smaller than 7; and R₄ has the samemeaning as defined in above chemical formula (I).)

It is preferable to use a solvent in the reaction. Illustrative examplesof solvents that may be used include lower alcohols (e.g., methanol,ethanol), acetonitrile, dichloromethane and dichloroethane, with the useof methanol or ethanol being preferred.

In cases where an acid is used, the acid may be, for example,hydrochloric acid, a substituted or unsubstituted benzenesulfonic acid,or acetic acid.

The reducing reaction may be carried out using a hydride reducingreagent such as sodium borohydride, sodium cyanoborohydride or sodiumtriacetoxyborohydride.

Alternatively, the reducing reaction may be carried out by a catalytichydrogenation reaction using a metal catalyst. Metal catalysts that maybe used include palladium, platinum rhodium, nickel and iron.

The reaction may be carried out at generally from 20 to 100° C.

(2) Compounds of the formula (Ia) may be synthesized from compounds ofthe following chemical formula (Va)

(wherein Ar and R₂ have the same meanings as defined in above chemicalformula (Ia).)

A compound of formula (Ia) can be obtained by reacting a compound offormula (Va) with a compound of the formula X—R₃R₄ (wherein R₃ and R₄have the same meanings as defined in above chemical formula (I), and Xis a halogen atom), either in the presence or absence of a base.

When the reaction is carried in the presence of a base, the base may be,for example, an alkali metal hydride such as sodium hydride, a carbonatesuch as potassium carbonate or sodium carbonate, an alkali metalhydroxide such as potassium hydroxide or sodium hydroxide, a tertiaryamine such as triethylamine, or a substituted or unsubstituted pyridinecompound such as pyridine or 4-dimethylaminopyridine. The use of analkali metal hydride such as sodium hydride is preferred.

The reaction may be carried out in the absence of a solvent or using asolvent which does not affect the reaction. In cases where a solvent isused, solvents such as amides (e.g., dimethylformamide,dimethylacetamide), nitriles (e.g., acetonitrile), sulfoxides (e.g.,dimethylsulfoxide), ethers (e.g., diethyl ether, tetrahydrofuran),esters (e.g., ethyl acetate, butyl acetate), aromatic hydrocarbons(e.g., benzene, xylene, toluene), alcohols (e.g., methanol, ethanol,propanol), ketones (e.g., acetone, methyl ethyl ketone), aliphatichydrocarbons (e.g., hexane, heptane, octane), halogenated hydrocarbons(e.g., dichloromethane, chloroform, chlorobenzene, dichlorobenzene), orwater may be used singly or as combinations of two or more thereof. Theuse of dimethylformamide, acetonitrile, an ether, dichloromethane orchloroform is preferred.

A compound of formula (Va) can be obtained by reacting a halide,anhydride, ester or the like of formula R₂ (wherein R₂ has the samemeaning as defined in above chemical compound (I)) with a compound offormula (IIIb), either in the presence or absence of a base.

The halide, anhydride, ester or the like of formula R₂ which is used maybe, for example, a carboxylic acid halide, a carboalkyloxy halide, asulfonyl halide, a O,O′-alkylphosphoryl halide, a carboxylic anhydride,a dialkyl dicarbonate, a carboxylic acid ester, a carbonic acid ester ora cyanohalide.

The reaction is preferably carried out using a solvent, in which casesolvents such as amides (e.g., dimethylformamide, dimethylacetamide),nitriles (e.g., acetonitrile), sulfoxides (e.g., dimethylsulfoxide),ethers (e.g., diethyl ether, tetrahydrofuran), esters (e.g., ethylacetate, butyl acetate), aromatic hydrocarbons (e.g., benzene, xylene,toluene), alcohols (e.g., methanol, ethanol, propanol), ketones (e.g.,acetone, methyl ethyl ketone), aliphatic hydrocarbons (e.g., hexane,heptane, octane), halogenated hydrocarbons (e.g., dichloromethane,chloroform, chlorobenzene, dichlorobenzene), or water may be used singlyor as combinations of two or more thereof. The use of an ether such asdiethyl ether or tetrahydrofuran is preferred.

When the reaction is carried in the presence of a base, the base may be,for example, an alkali metal hydride such as sodium hydride, a carbonatesuch as potassium carbonate or sodium carbonate, an alkali metalhydroxide such as potassium hydroxide or sodium hydroxide, a tertiaryamine such as triethylamine, or a substituted or unsubstituted pyridinecompound such as pyridine or 4-dimethylaminopyridine.

A compound of formula (Va) can be obtained by reacting a compound offormula R₂—NH₂ (wherein R₂ has the same meaning as defined in abovechemical compound (I)) with a compound of formula (IIIa), either in thepresence or absence of a base.

The use of a solvent in the reaction is preferred, in which casesolvents such as amides (e.g., dimethylformamide, dimethylacetamide),nitriles (e.g., acetonitrile), sulfoxides (e.g., dimethylsulfoxide),ethers (e.g., diethyl ether, tetrahydrofuran), esters (e.g., ethylacetate, butyl acetate), aromatic hydrocarbons (e.g., benzene, xylene,toluene), alcohols (e.g., methanol, ethanol, propanol), ketones (e.g.,acetone, methyl ethyl ketone), aliphatic hydrocarbons (e.g., hexane,heptane, octane), halogenated hydrocarbons (e.g., dichloromethane,chloroform, chlorobenzene, dichlorobenzene), or water may be used singlyor as combinations of two or more thereof. The use of acetonitrile orthe like is preferred.

When the reaction is carried in the presence of a base, the base may be,for example, an alkali metal hydride such as sodium hydride, a carbonatesuch as potassium carbonate or sodium carbonate, an alkali metalhydroxide such as potassium hydroxide or sodium hydroxide, a tertiaryamine such as triethylamine, or a substituted or unsubstituted pyridinecompound such as pyridine or 4-dimethylaminopyridine.

(3) Compounds of the formula (Ia) may also be synthesized from compoundsof the following chemical formula (Vb)

(wherein R₂, R₃ and R₄ have the same meanings as defined in abovechemical formula (I)).

Compounds of the formula (Ia) can be obtained by reacting a compound ofthe formula (Vb) with a compound of the formula Ar—CH₂—X (wherein Ar hasthe same meaning as defined in above chemical formula (I), and X is ahalogen atom, OTs or OMs), either in the presence or absence of a base.

When the reaction is carried in the presence of a base, the base may be,for example, an alkali metal hydride such as sodium hydride, a carbonatesuch as potassium carbonate or sodium carbonate, an alkali metalhydroxide such as potassium hydroxide or sodium hydroxide, a tertiaryamine such as triethylamine, or a substituted or unsubstituted pyridinecompound such as pyridine or 4-dimethylaminopyridine. The use of analkali metal hydride such as sodium hydride is preferred.

The reaction may be carried out in the absence of a solvent or using asolvent which does not affect the reaction. In cases where a solvent isused, solvents such as amides (e.g., dimethylformamide,dimethylacetamide), nitriles (e.g., acetonitrile), sulfoxides (e.g.,dimethylsulfoxide), ethers (e.g., diethyl ether, tetrahydrofuran),esters (e.g., ethyl acetate, butyl acetate), aromatic hydrocarbons(e.g., benzene, xylene, toluene), alcohols (e.g., methanol, ethanol,propanol), ketones (e.g., acetone, methyl ethyl ketone), aliphatichydrocarbons (e.g., hexane, heptane, octane), halogenated hydrocarbons(e.g., dichloromethane, chloroform, chlorobenzene, dichlorobenzene), orwater may be used singly or as combinations of two or more thereof. Theuse of dimethylformamide, acetonitrile, an ether, dichloromethane orchloroform is preferred.

The compound of formula (Vb) may be obtained by reacting a halide,anhydride, ester or the like of the formula R₂ (wherein R₂ has the samemeaning as defined in above chemical formula (I)) with a compound of theformula (IVa), either in the presence or absence of a base.

Examples of halides, anhydrides and esters of the formula R₂ that may beused include carboxylic acid halides, carboalkyloxy halides, sulfonylhalides, O,O′-alkylphosphoryl halides, carboxylic anhydrides, dialkyloxydicarbonates, carboxylic acid esters, carbonic acid esters and cyanogenhalides.

The use of a solvent in the reaction is preferred. Solvents such asamides (e.g., dimethylformamide, dimethylacetamide), nitriles (e.g.,acetonitrile), sulfoxides (e.g., dimethylsulfoxide), ethers (e.g.,diethyl ether, tetrahydrofuran), esters (e.g., ethyl acetate, butylacetate), aromatic hydrocarbons (e.g., benzene, xylene, toluene),alcohols (e.g., methanol, ethanol, propanol), ketones (e.g., acetone,methyl ethyl ketone), aliphatic hydrocarbons (e.g., hexane, heptane,octane), halogenated hydrocarbons (e.g., dichloromethane, chloroform,chlorobenzene, dichlorobenzene), or water may be used singly or ascombinations of two or more thereof. The use of an ether such as diethylether or tetrahydrofuran is preferred.

When the reaction is carried in the presence of a base, the base may be,for example, an alkali metal hydride such as sodium hydride, a carbonatesuch as potassium carbonate or sodium carbonate, an alkali metalhydroxide such as potassium hydroxide or sodium hydroxide, a tertiaryamine such as triethylamine, or a substituted or unsubstituted pyridinecompound such as pyridine or 4-dimethylaminopyridine.

Alternatively, the compound of formula (Vb) can be obtained by reactinga compound of the formula R₂—NH₂ (wherein R₂ has the same meaning asdefined in above chemical compound (I)) with a compound of the formulaX—R₃R₄ (wherein R₃ and R₄ have the same meanings as defined in abovechemical formula (I), and X is a halogen atom), either in the presenceor absence of a base.

The use of a solvent in the reaction is preferred. Solvents such asamides (e.g., dimethylformamide, dimethylacetamide), nitriles (e.g.,acetonitrile), sulfoxides (e.g., dimethylsulfoxide), ethers (e.g.,diethyl ether, tetrahydrofuran), esters (e.g., ethyl acetate, butylacetate), aromatic hydrocarbons (e.g., benzene, xylene, toluene),alcohols (e.g., methanol, ethanol, propanol), ketones (e.g., acetone,methyl ethyl ketone), aliphatic hydrocarbons (e.g., hexane, heptane,octane), halogenated hydrocarbons (e.g., dichloromethane, chloroform,chlorobenzene, dichlorobenzene), or water may be used singly or ascombinations of two or more thereof. The use of acetonitrile ortetrahydrofuran is preferred.

When the reaction is carried in the presence of a base, the base may be,for example, an alkali metal hydride such as sodium hydride, a carbonatesuch as potassium carbonate or sodium carbonate, an alkali metalhydroxide such as potassium hydroxide or sodium hydroxide, a tertiaryamine such as triethylamine, or a substituted or unsubstituted pyridinecompound such as pyridine or 4-dimethylaminopyridine.

(4) Compounds of the chemical formula (Ib) below can be obtained byreacting a compound of the formula ArCH₂X (wherein X is a halogen atom)with a compound of the formula R₂NH₂ (wherein R₂ has the same meaning asdefined in above chemical compound (I)), either in the presence orabsence of a base.

(In the formula, Ar and R₂ have the same meanings as defined in abovechemical formula (I).)

When the reaction is carried in the presence of a base, the base may be,for example, an alkali metal hydride such as sodium hydride, a carbonatesuch as potassium carbonate or sodium carbonate, an alkali metalhydroxide such as potassium hydroxide or sodium hydroxide, a tertiaryamine such as triethylamine, or a substituted or unsubstituted pyridinecompound such as pyridine or 4-dimethylaminopyridine.

The reaction may be carried out in the absence of a solvent or using asolvent which does not affect the reaction. In cases where a solvent isused, solvents such as amides (e.g., dimethylformamide,dimethylacetamide), nitriles (e.g., acetonitrile), sulfoxides (e.g.,dimethylsulfoxide), ethers (e.g., diethyl ether, tetrahydrofuran),esters (e.g., ethyl acetate, butyl acetate), aromatic hydrocarbons(e.g., benzene, xylene, toluene), alcohols (e.g., methanol, ethanol,propanol), ketones (e.g., acetone, methyl ethyl ketone), aliphatichydrocarbons (e.g., hexane, heptane, octane), or halogenatedhydrocarbons (e.g., dichloromethane, chloroform, chlorobenzene,dichlorobenzene) may be used singly or as combinations of two or morethereof. The use of acetonitrile is preferred.

The reaction may be carried out at generally from 0 to 200° C., althoughit is preferable to add the reagent at 20 to 40° C., and to carry outthe reaction at 60 to 80° C.

(5) Compounds of the following chemical formula (Ic)

(wherein R₁ is a C₁₋₆ alkyl group, and Ar, R₂, R₃ and R₄ having the samemeanings as defined in above chemical formula (I)) can be obtained byreacting a halide, anhydride, ester or the like of the formula R₂ (R₂having the same meaning as defined in above chemical formula (I)) with acompound of the formula (VIa) below, either in the presence or absenceof a base.

(In the formula, R₁ is a C₁₋₆ alkyl group, and Ar, R₃ and R₄ have thesame meanings as defined in above chemical formula (I).)

Examples of halides, anhydrides and esters of the formula R₂ which maybe used include carboxylic acid halides, carboalkyloxy halides, sulfonylhalides, O,O′-alkylphosphoryl halides, carboxylic anhydrides, dialkyldicarbonates, carboxylic acid esters and carbonic acid esters. The useof, for example, acetyl chloride, ethyl chloroformate, methanesulfonylchloride, diethyl chlorophosphate, trifluoroacetic anhydride or ethylformate is preferred.

When the reaction is carried in the presence of a base, the base may be,for example, an alkali metal hydride such as sodium hydride, a carbonatesuch as potassium carbonate or sodium carbonate, an alkali metalhydroxide such as potassium hydroxide or sodium hydroxide, a tertiaryamine such as triethylamine, or a substituted or unsubstituted pyridinecompound such as pyridine or 4-dimethylaminopyridine.

The reaction may be carried out in the absence of a solvent or using asolvent which does not affect the reaction. In cases where a solvent isused, solvents such as amides (e.g., dimethylformamide,dimethylacetamide), nitriles (e.g., acetonitrile), sulfoxides (e.g.,dimethylsulfoxide), ethers (e.g., diethyl ether, tetrahydrofuran),esters (e.g., ethyl acetate, butyl acetate), aromatic hydrocarbons(e.g., benzene, xylene, toluene), alcohols (e.g., methanol, ethanol,propanol), ketones (e.g., acetone, methyl ethyl ketone), aliphatichydrocarbons (e.g., hexane, heptane, octane), halogenated hydrocarbons(e.g., dichloromethane, chloroform, chlorobenzene, dichlorobenzene), orwater may be used singly or as combinations of two or more thereof. Theuse of dimethylformamide, acetonitrile, ethers, dichloromethane orchloroform is preferred.

The reaction may be carried out at generally from −80 to 100° C.,although it is preferable to carry out the reaction in the range of 20to 50° C.

When the alkyl moiety of R₂ in the compound of formula (Ic) is a C₁₋₆alkyl carbonyl group which may be substituted with a halogen atom, thecompound of formula (Ic) can be obtained by reacting a carboxylic acidof the formula R_(2′)—COOH (wherein R_(2′) is a C₁₋₆ alkyl group whichmay be substituted with a halogen atom) with a compound of the formula(VIa) in the presence of a dehydration-condensation agent.

A carbodiimide compound such as dicyclohexylcarbodiimide or1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride may be usedas the dehydration-condensation agent.

The reaction is preferably carried out using a solvent. Solvents such asamides (e.g., dimethylformamide, dimethylacetamide), nitriles (e.g.,acetonitrile), sulfoxides (e.g., dimethylsulfoxide), ethers (e.g.,diethyl ether, tetrahydrofuran), esters (e.g., ethyl acetate, butylacetate), aromatic hydrocarbons (e.g., benzene, xylene, toluene),ketones (e.g., acetone, methyl ethyl ketone), aliphatic hydrocarbons(e.g., hexane, heptane, octane), or halogenated hydrocarbons (e.g.,dichloromethane, chloroform, chlorobenzene, dichlorobenzene) may be usedsingly or as combinations of two or more thereof. The use ofdichloromethane or chloroform is preferred.

The reaction may be carried out at generally from −80 to 100° C.,although it is preferable to carry out the reaction in the range of 20to 50° C.

When R₂ in the compound of formula (Ic) is a cyano group, the compoundof formula (Ic) may be obtained by reacting a known cyanating reagentwith the compound of formula (IVa), either in the presence or absence ofa base.

Cyanating reagents which may be used for this purpose include cyanogenbromide, cyanogen iodide, 1-cyanoimidazole, 1-cyanobenzotriazole, andsubstituted and unsubstituted benzenesulfonyl cyanide.

When the reaction is carried out in the presence of a base, the baseused for this purpose may be, for example, an alkali metal hydride suchas sodium hydride, a carbonate such as potassium carbonate or sodiumcarbonate, an alkali metal acetate such as sodium acetate, a tertiaryamine such as triethylamine, or a substituted or unsubstituted pyridinecompound such as pyridine or 4-dimethylaminopyridine.

The reaction may be carried out in the absence of a solvent or using asolvent which does not affect the reaction. In cases where a solvent isused, solvents such as amides (e.g., dimethylformamide,dimethylacetamide), nitriles (e.g., acetonitrile), sulfoxides (e.g.,dimethylsulfoxide), ethers (e.g., diethyl ether, tetrahydrofuran),esters (e.g., ethyl acetate, butyl acetate), aromatic hydrocarbons(e.g., benzene, xylene, toluene), alcohols (e.g., methanol, ethanol,propanol), ketones (e.g., acetone, methyl ethyl ketone), aliphatichydrocarbons (e.g., hexane, heptane, octane), halogenated hydrocarbons(e.g., dichloromethane, chloroform, chlorobenzene, dichlorobenzene), orwater may be used singly or as combinations of two or more thereof. Theuse of an ether such as diethyl ether or tetrahydrofuran, or ahalogenated hydrocarbon such as dichloromethane and chloroform ispreferred.

The reaction may be carried out at generally from 0 to 100° C., althoughit is preferable to add the cyanating reagent at 0° C. and graduallyraise the temperature to about 20 to 50° C.

The compound of formula (VIa) can be obtained by adding a compound ofthe formula H₂N—R₃R₄ (wherein R₃ and R₄ have the same meanings asdefined in chemical formula (I)) to a compound of the following chemicalformula (VII)

(wherein R₁ is the same as above) in the presence or absence of an acidso as to form an imine, then carrying out a reducing reaction.

The reaction is preferably carried out using a solvent. It is preferableto use a lower alcohol such as methanol or ethanol, or dichloromethaneor chloroform as the solvent, although the use of acetonitrile is alsopossible.

When an acid is used, the acid may be, for example, hydrochloride acid,a substituted or unsubstituted benzenesulfonic acid, or acetic acid.

The reducing reaction may be carried out using a hydride reducingreagent such as sodium borohydride, sodium cyanoborohydride or sodiumtriacetoxyborohydride.

The reducing reaction may be carried out by a catalyst hydrogenationreaction using a metal catalyst. Metal catalysts that may be usedinclude palladium, platinum, rhodium, nickel and iron.

The reaction may be carried out at a temperature in the range ofgenerally from 20 to 100° C.

(6) Compounds of the following chemical formula (Id)

(wherein Ar, R₂ and R₈ have the same meanings as defined in abovechemical formula (I)) can be obtained by reacting carbon disulfide and acompound of the formula R₈—X (wherein R₈ has the same meaning as definedin above chemical formula (I), and X is a halogen atom), in the presenceof a base, with a compound of the chemical formula (VIII) below that canbe synthesized by a method described in the literature (Journal ofMedicinal Chemistry 42(12), 2227-2234 (1999)).

(In the formula, Ar has the same meaning as defined in above chemicalformula (I).)

The base used for this purpose may be, for example, an alkali metalhydride such as sodium hydride, a carbonate such as potassium carbonateor copper carbonate, an alkali metal hydroxide such as potassiumhydroxide or sodium hydroxide, a metal oxide such as copper oxide ormagnesium oxide, a tertiary amine such as triethylamine, or asubstituted or unsubstituted pyridine compound such as pyridine or4-dimethylaminopyridine. The use of a strong base such as potassiumt-butylate is preferred.

The reaction may be carried out in the absence of a solvent or using asolvent which does not affect the reaction. In cases where a solvent isused, solvents such as amides (e.g., dimethylformamide,dimethylacetamide), nitriles (e.g., acetonitrile), sulfoxides (e.g.,dimethylsulfoxide), ethers (e.g., diethyl ether, tetrahydrofuran),esters (e.g., ethyl acetate, butyl acetate), aromatic hydrocarbons(e.g., benzene, xylene, toluene), alcohols (e.g., methanol, ethanol,propanol), ketones (e.g., acetone, methyl ethyl ketone), aliphatichydrocarbons (e.g., hexane, heptane, octane), halogenated hydrocarbons(e.g., dichloromethane, chloroform, chlorobenzene, dichlorobenzene), orwater may be used singly or as combinations of two or more thereof. Theuse of an ether such as tetrahydrofuran is preferred.

The reaction may be carried out at generally from −80 to 100° C.,although it is preferable to carry out the reaction in the range of 20to 50° C.

A compound of the chemical formula (Ie)

(wherein Ar, R₁, Y and R_(4e) are the same as defined above) can beobtained by reacting a compound of the formula (IX) below with acompound of the formula ArCH(R₁)X (wherein Ar and R₁ are the same asdefined above, and X is a halogen, OTs or OMs), in the presence orabsence of a base.

(In the reaction, Y and R_(4e) are the same as defined above.)

When the reaction is carried out in the presence of a base, the base maybe, for example, an alkali metal hydride such as sodium hydride, acarbonate such as potassium carbonate or sodium carbonate, an alkalimetal hydroxide such as potassium hydroxide or sodium hydroxide, atertiary amine such as triethylamine, or a substituted or unsubstitutedpyridine compound such as pyridine or 4-dimethylaminopyridine.

The reaction may be carried out in the absence of a solvent or using asolvent which does not affect the reaction. In cases where a solvent isused, solvents such as amides (e.g., dimethylformamide,dimethylacetamide), nitriles (e.g., acetonitrile), sulfoxides (e.g.,dimethylsulfoxide), ethers (e.g., diethyl ether, tetrahydrofuran),esters (e.g., ethyl acetate, butyl acetate), aromatic hydrocarbons(e.g., benzene, xylene, toluene), alcohols (e.g., methanol, ethanol,propanol), ketones (e.g., acetone, methyl ethyl ketone), aliphatichydrocarbons (e.g., hexane, heptane, octane), or halogenatedhydrocarbons (e.g., dichloromethane, chloroform, chlorobenzene,dichlorobenzene) may be used singly or as combinations of two or morethereof. The use of acetonitrile is preferred.

The reaction may be carried out at generally from 0 to 200° C., althoughit is preferable to add the reagent at 20 to 40° C., and carry out thereaction at 60 to 80° C.

Compounds of the above chemical formula (IX) can be obtained by reactinga compound of the formula R_(4e)—C(═O)X, R_(4e)—C(═O)OC(═O)R_(4e) orR_(4e)C(═O)OR′ (wherein X is a halogen atom, OTS or OMs; R′ is a C₁₋₆alkyl group; and R_(4e) is as defined above) with a compound of theformula (IXa) below, either in the presence or absence of a base.

(In the formula, Y is as defined above.)

When the reaction is carried out in the presence of a base, the base maybe, for example, an alkali metal hydride such as sodium hydride, acarbonate such as potassium carbonate or sodium carbonate, an alkalimetal hydroxide such as potassium hydroxide or sodium hydroxide, atertiary amine such as triethylamine, or a substituted or unsubstitutedpyridine compound such as pyridine or 4-dimethylaminopyridine.

The reaction may be carried out in the absence of a solvent or using asolvent which does not affect the reaction. In cases where a solvent isused, solvents such as amides (e.g., dimethylformamide,dimethylacetamide), nitriles (e.g., acetonitrile), sulfoxides (e.g.,dimethylsulfoxide), ethers (e.g., diethyl ether, tetrahydrofuran),esters (e.g., ethyl acetate, butyl acetate), aromatic hydrocarbons(e.g., benzene, xylene, toluene), alcohols (e.g., methanol, ethanol,propanol), ketones (e.g., acetone, methyl ethyl ketone), aliphatichydrocarbons (e.g., hexane, heptane, octane), halogenated hydrocarbons(e.g., dichloromethane, chloroform, chlorobenzene, dichlorobenzene), orwater may be used singly or as combinations of two or more thereof. Theuse of dimethylformamide, acetonitrile, ethers, dichloromethane orchloroform is preferred.

The reaction may be carried out at generally from −80 to 100° C.,although it is preferable to carry out the reaction in the range of 20to 50° C.

The compound of above formula (IX) may also be obtained by reacting acompound of above formula (IXa) with a carboxylic acid of the formulaR_(4e)—COOH (wherein R_(4e) is the same as defined above) using adehydration-condensation agent, either in the presence or absence of abase.

A carbodiimide compound such as dicyclohexylcarbodiimide or1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride may be usedas the dehydration-condensation agent.

When the reaction is carried out in the presence of a base, the base maybe, for example, a carbonate such as potassium carbonate or sodiumcarbonate, a tertiary amine such as triethylamine, or a substituted orunsubstituted pyridine compound such as pyridine or4-dimethylaminopyridine.

The reaction is preferably carried out using a solvent. For example,amides (e.g., dimethylformamide, dimethylacetamide), nitriles (e.g.,acetonitrile), sulfoxides (e.g., dimethylsulfoxide), ethers (e.g.,diethyl ether, tetrahydrofuran), esters (e.g., ethyl acetate, butylacetate), aromatic hydrocarbons (e.g., benzene, xylene, toluene),ketones (e.g., acetone, methyl ethyl ketone), aliphatic hydrocarbons(e.g., hexane, heptane, octane), or halogenated hydrocarbons (e.g.,dichloromethane, chloroform, chlorobenzene, dichlorobenzene) may be usedsingly or as combinations of two or more thereof. The use ofdichloromethane or chloroform is preferred.

The reaction may be carried out at generally from −80 to 100° C.,although it is preferable to carry out the reaction in the range of 20to 50° C.

Compounds of above formula (Ie) can be obtained by reacting a compoundof the formula R_(4e)—C(═O)X, R_(4e)—C(═O)OC(═O)R_(4e) orR_(4e)—C(═O)OR′ (wherein X is a halogen atom, R′ is a C₁₋₆ alkyl group,and R_(4e) is as defined above) with a compound of the formula (IXb)below or a salt thereof, in the presence or absence of a base.

(In the formula, Ar, R₁ and Y are as defined above.)

When the reaction is carried out in the presence of a base, the base maybe, for example, an alkali metal hydride such as sodium hydride, acarbonate such as potassium carbonate or sodium carbonate, an alkalimetal hydroxide such as potassium hydroxide or sodium hydroxide, atertiary amine such as triethylamine, or a substituted or unsubstitutedpyridine compound such as pyridine or 4-dimethylaminopyridine.

The reaction may be carried out in the absence of a solvent or using asolvent which does not affect the reaction. In cases where a solvent isused, solvents such as amides (e.g., dimethylformamide,dimethylacetamide), nitriles (e.g., acetonitrile), sulfoxides (e.g.,dimethylsulfoxide), ethers (e.g., diethyl ether, tetrahydrofuran),esters (e.g., ethyl acetate, butyl acetate), aromatic hydrocarbons(e.g., benzene, xylene, toluene), alcohols (e.g., methanol, ethanol,propanol), ketones (e.g., acetone, methyl ethyl ketone), aliphatichydrocarbons (e.g., hexane, heptane, octane), halogenated hydrocarbons(e.g., dichloromethane, chloroform, chlorobenzene, dichlorobenzene), orwater may be used singly or as combinations of two or more thereof. Theuse of dimethylformamide, acetonitrile, ethers, dichloromethane orchloroform is preferred.

The reaction may be carried out at generally from −80 to 100° C.,although it is preferable to carry out the reaction in the range of 20to 50° C.

Compounds of above formula (Ie) may also be obtained by reacting acompound of the above formula (IXb) or a salt thereof with a carboxylicacid of the formula R_(4e)—COOH (wherein R_(4e) is as defined above)using a dehydration-condensation agent, either in the presence orabsence of a base.

A carbodiimide compound such as dicyclohexylcarbodiimide or1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride may be usedas the dehydration-condensation agent.

When the reaction is carried out in the presence of a base, the base maybe, for example, a carbonate such as potassium carbonate or sodiumcarbonate, a tertiary amine such as triethylamine, or a substituted orunsubstituted pyridine compound such as pyridine or4-dimethylaminopyridine.

The reaction is preferably carried out using a solvent. For example,amides (e.g., dimethylformamide, dimethylacetamide), nitriles (e.g.,acetonitrile), sulfoxides (e.g., dimethylsulfoxide), ethers (e.g.,diethyl ether, tetrahydrofuran), esters (e.g., ethyl acetate, butylacetate), aromatic hydrocarbons (e.g., benzene, xylene, toluene),ketones (e.g., acetone, methyl ethyl ketone), aliphatic hydrocarbons(e.g., hexane, heptane, octane), or halogenated hydrocarbons (e.g.,dichloromethane, chloroform, chlorobenzene, dichlorobenzene) may be usedsingly or as combinations of two or more thereof. The use ofdichloromethane or chloroform is preferred.

The reaction may be carried out at generally from −80 to 100° C.,although it is preferable to carry out the reaction in the range of 20to 50° C.

Compounds of the above formula (IXb) can be obtained by reacting acompound of above formula (IXa) with a compound of the formula ArCH(R₁)X(wherein Ar, R₁ and X are as defined above), in the presence or absenceof a base.

When the reaction is carried out in the presence of a base, the base maybe, for example, an alkali metal hydride such as sodium hydride, acarbonate such as potassium carbonate or sodium carbonate, an alkalimetal hydroxide such as potassium hydroxide or sodium hydroxide, atertiary amine such as triethylamine, or a substituted or unsubstitutedpyridine compound such as pyridine or 4-dimethylaminopyridine.

The reaction may be carried out in the absence of a solvent or using asolvent which does not affect the reaction. In cases where a solvent isused, solvents such as amides (e.g., dimethylformamide,dimethylacetamide), nitriles (e.g., acetonitrile), sulfoxides (e.g.,dimethylsulfoxide), ethers (e.g., diethyl ether, tetrahydrofuran),esters (e.g., ethyl acetate, butyl acetate), aromatic hydrocarbons(e.g., benzene, xylene, toluene), alcohols (e.g., methanol, ethanol,propanol), ketones (e.g., acetone, methyl ethyl ketone), aliphatichydrocarbons (e.g., hexane, heptane, octane), halogenated hydrocarbons(e.g., dichloromethane, chloroform, chlorobenzene, dichlorobenzene), orwater may be used singly or as combinations of two or more thereof. Theuse of dimethylformamide, acetonitrile, ethers, dichloromethane orchloroform is preferred.

The reaction may be carried out at generally from −80 to 100° C.,although it is preferable to carry out the reaction in the range of 20to 50° C.

In cases where (Ie) is synthesized via (IX) from a compound of chemicalformula (IXa), or in cases where (Ie) is synthesized via (IXb) from acompound of chemical formula (IXa), the reactions may be carried outconsecutively without removing the (IX) or (IXb), or the reactions from(IXa) to (Ie) may be allowed to proceed simultaneously within the samereaction vessel.

EXAMPLES

Next, the invention is described more fully below by way of workingexamples, although the invention is not limited by the working examples.

Reference Example 12-chloro-5-[N-(2-methylthioethyl)]aminomethylpyridine (Compound 23)

2-methylthioethylamine (3.0 g, 33 mmol) was dissolved in 25 mL ofanhydrous dimethylformamide, following which 5.3 g (33 mmol) of2-chloro-5-chloromethylpyridine, 1.6 g of 60% sodium hydride (netweight, 950 mg; 40 mmol) were added in this order, and stirring at 70°C. was carried out for 90 minutes. The reaction mixture was cooled to 0°C. and the reaction was brought to completion by adding about 30 mL ofwater a little at a time, after which the reaction mixture was extractedtwice with about 50 mL of dichloromethane. The dichloromethane phase wasdried over anhydrous magnesium sulfate, concentrated, and subsequentlypurified by silica gel column chromatography (hexane/ethylacetate=1:1→ethylacetate→dichloromethane/methanol=1:19→dichloromethane/methanol=1:10),giving 4.6 g of the target compound (yield, 64%).

Synthesis Example 12-chloro-5-[N-cyano-N-(2-methylthioethyl)]aminomethylpyridine (Compound1)

Anhydrous diethyl ether, 4 mL, was added to 123 mg (1.16 mmol) ofcyanogen bromide, and the mixture was cooled to 0° C. To this wereadded, in order, 250 mg (1.16 mmol) of2-chloro-5-[N-(2-methylthioethyl)]aminomethylpyridine (ReferenceExample 1) dissolved in 3 mL of anhydrous diethyl ether, and 95 mg (1.16mmol) of sodium acetate, following which the system was stirredovernight at room temperature. Next, about 10 mL of a 1% aqueoussolution of sodium hydroxide was added to the reaction mixture and themixture was stirred for 1 hour, following which about 20 mL of diethylether was added and liquid-liquid extraction was carried out. Thediethyl ether phase was washed with, in order, about 10 mL of water andabout 10 mL of 1% hydrochloric acid, then dried over anhydrous magnesiumsulfate and concentrated under reduced pressure, giving 209 mg of thetarget compound (yield, 75%).

Synthesis Example 22-chloro-5-[N-formyl-N-(2-methylthioethyl)]aminomethylpyridine (Compound29)

Ethyl formate (10 mL) was added to 132 mg (0.61 mmol) of2-chloro-5-[N-(2-methylthio)ethyl]aminomethylpyridine (Reference Example1), and the system was refluxed for 3 hours. Once the reaction mixturehad returned to room temperature, the solvent was distilled off underreduced pressure, and purification was carried out with silica gelcolumn chromatography (hexane/ethyl acetate=7:3→1:1), giving 159 mg ofthe target compound (yield, 81%).

Synthesis Example 32-chloro-5-[N-trifluoroacetyl-N-ethyl]aminomethylpyridine (Compound 21)

A solution of 140 mg (0.67 mmol) of trifluoroacetic anhydride dissolvedin 5 mL of anhydrous dichloromethane was added dropwise under icecooling to a solution of 120 mg (0.70 mmol) ofethyl-(2-chloro-5-pyridylmethyl)amine synthesized by the methoddescribed in U.S. Patent Application Publication No. 2009306041 and 101mg (1 mmol) of triethylamine dissolved in 5 mL of anhydrousdichloromethane. Following dropwise addition, the system was stirredovernight at room temperature, then the reaction mixture was washedwith, in order, ice-cooled 1% aqueous sodium hydroxide, water, 1%hydrochloric acid, then water, and subsequently dried over anhydrousmagnesium sulfate. The solvent was distilled off under reduced pressure,giving 107 mg the target compound (yield, 78%).

Synthesis Example 42-chloro-5-(N-cyano-N-2-isopropyl)aminomethylpyridine (Compound 15)

Acetone (2 mL) and 1 mL of methanol were added to 50 mg (0.26 mmol) of2-chloro-5-aminoethylpyridine, 43 mg (0.52 mmol) of sodium acetate wasadded, and the mixture was stirred at room temperature for 4 hours.Next, 30 mg (0.78 mmol) of sodium borohydride was added, and the mixturewas stirred at room temperature for 1 hour. The reaction mixture wasfiltered and then concentrated, after which ethyl acetate and water wereadded and liquid-liquid extraction was carried out. The organic phasewas dried over anhydrous magnesium sulfate, then concentrated andsubsequently purified on a preparative TLC plate, giving 17 mg of2-chloro-5-[N-(2-isopropylaminomethyl)]pyridine (yield, 36%).

Using 57 mg of the resulting2-chloro-5-[N-(2-isopropylaminomethyl)]pyridine, 54 mg of the targetcompound (yield, 47%) was obtained by the method described in SynthesisExample 1.

Synthesis Example 52-chloro-5-[N-cyano-N-(2-propargyl)]aminomethylpyridine (Compound 42)

2-chloro-5-aminoethylpyridine (1.50 g, 10.6 mmol) was dissolved in 10 mLof anhydrous dimethylformamide, then 486 mg (net weight, 292 mg; 12.7mmol) of 60% sodium hydride and 1.25 g (10.6 mmol) of propargyl bromidewere added in this order, and stirring was carried out at 70° C. for 3.5hours. The reaction mixture was returned to room temperature and thereaction was stopped by slowly adding water, after which the reactionmixture was extracted with ethyl acetate. The ethyl acetate phase wasdried over anhydrous magnesium sulfate and subsequently concentrated,then purified by silica gel column chromatography (hexane/ethylacetate=1:1), giving 892 mg of2-chloro-5-[N-(2-propargyl)]aminomethylpyridine (yield, 47%).

Using 60 mg of the resulting2-chloro-5-[N-(2-propargyl)]aminomethylpyridine, 20 mg of the targetcompound (yield, 30%) was obtained by the method described in SynthesisExample 1.

Synthesis Example 62-chloro-5-[N-cyano-N-(6-chloro-3-pyridylmethyl)]aminomethylpyridine(Compound 17)

6-chloro-3-chloromethylpyridine (648 mg, 4 mmol), 50% aqueous ammoniumcyanide solution (100 mg), and potassium carbonate (590 mg, 5 mmol) weresuspended in acetonitrile (20 mL), and the mixture was refluxed underheating for 40 hours. The condensate was filtered while hot, thefiltrate was concentrated, and the residue was washed with ether andwater. The viscous mixture was recrystallized from a small amount ofmethanol, giving 28 mg of the target compound.

¹H-NMR (CDCl₃, δ, ppm): 4.17 (4H, s), 7.40 (2H, d), 7.68 (2H, dd), 8.31(2H, d)

IR: 2207 (CN)

MS: m/z=293 (M+H)

Synthesis Example 74-chloro-[N-cyano-N-(4-chlorobenzyl)]aminomethylbenzene (Compound 55)

The target compound was obtained in an amount of 450 mg (yield, 15%)from 1.61 g of 4-chlorobenzyl chloride by the same method as inSynthesis Example 6.

¹H-NMR (CDCl₃, δ, ppm): 4.10 (2H, s), 7.23 (2H, d), 7.36 (2H, d)

MS: m/z=291 (M+H)

Synthesis Example 8 N-[1-(6-chloro-3-pyridyl)ethyl]-N-cyanoethylamino(Compound 18)

6-chloro-3-acetylpyridine (1.03 g, 0.3 mmol) and a 30%ethylamine-methanol solution (1.0 mL) were mixed with 8 mL ofchloroform, and the mixture was subjected to refluxing. After 8 hours, 1mL of 30% ethylamine-methanol solution was added and stirring wascontinued for 12 hours at the same temperature. The chloroform wasdistilled off and the residue was dissolved in 10 mL of methanol, thenice-cooled. Sodium borohydride (1 g) was added a little at a time, andthe system was stirred overnight. The methanol was distilled off, andthe residue was extracted with acetonitrile. The extract was thenconcentrated under reduced pressure. Acetonitrile extraction andconcentration under reduced pressure were each repeated another twotimes, following which the residue was dissolved in chloroform, washedwith 1% aqueous NaOH, and the chloroform phase was dried over solid KOH.The chloroform was distilled off under reduced pressure, giving 790 mgof crude N-[1-(6-chloro-3-pyridyl)ethyl]-N-ethylamine product (purity,80%).

Using 100 mg of the crude N-[1-(6-chloro-3-pyridyl)ethyl]-N-ethylaminethus obtained, 55 mg (yield, 60%) of the target product was obtained bythe method described in Synthesis Example 1.

¹H-NMR (CDCl₃, δ, ppm): 1.25 (3H, t), 1.66 (3H, d), 2.91 (2H, m), 4.14(1H, q), 7.37 (1H, d), 7.73 (1H, dd), 8.30 (1H, d)

IR: 2211 (CN), 2206 (CN)

Synthesis Example 9 2-[N-(6-chloro-3-pyridylmethyl)cyanamide]ethylmethylcarbonotrithioate (Compound 6)

Potassium t-butylate (112 mg, 1 mmol) was added to a solution of(6-chloro-3-pyridylmethyl)-2-imino-1,3-thiazolidine (228 mg, 1 mmol),synthesized by a method described in the literature (Journal ofMedicinal Chemistry, 42(12), 2227 (1999)), in 15 mL of tetrahydrofuran,and the mixture was stirred for 30 minutes at room temperature,following which 228 mg (3 mmol) of carbon disulfide was added a littleat a time and stirring was continued for 1 hour. Methyl iodide (142 mg,1 mmol) was added dropwise and the system was stirred for 2 hours. Theinsoluble solid was removed by filtration through Celite, and thefiltrate was concentrated under reduced pressure. The target compoundwas isolated as a yellow oil from the viscous residue by silica gelcolumn chromatography using ethyl acetate/hexane (1:1 volumetric ratio)as the developing solvent. The yield was 130 mg (41%).

¹H-NMR (CDCl₃, δ, ppm): 2.76 (3H, s), 3.31 (2H, t), 3.63 (2H, t), 4.28(2H, s), 7.38 (1H, d), 7.73 (1H, dd), 8.35 (1H, d)

IR: 2211 (CN)

Synthesis Example 102-chloro-5-[N-trifluorosulfonyl-N-(2-propynyl)]aminomethylpyridine(Compound 152)

An amount of 104 mg (0.58 mmol) of2-chloro-5-[N-(2-propynyl)]aminomethylpyridine obtained by the methoddescribed in Synthesis Example 5 was dissolved in 10 mL of anhydrousdichloromethane, 191 μL (1.16 mmol, 326 mg) of trifluorosulfonicanhydride was added, and the mixture was stirred at room temperature for2 hours. After reaction completion, the reaction mixture was diluted byadding dichloromethane, then washed with, in order, a 1% aqueous sodiumhydroxide solution and a 1% aqueous hydrochloric acid solution, andsubsequently dried over anhydrous magnesium sulfate, concentrated underreduced pressure, and purified by silica gel column chromatography(hexane/ethyl acetate=2:8), giving 55 mg of the target compound (yield,30%).

Synthesis Example 112-chloro-5-[N-cyano-N-(cyclopropylmethyl)]aminomethylpyridine (Compound71)

The N-[(6-chloropyridin-3-yl)methyl]cyanamide (30 mg, 0.18 mL)synthesized by the method in a comparative example was dissolved in 3 mLof anhydrous dimethylformamide, 10 mg of 60% sodium hydride (net weight,6 mg; 0.26 mmol) was added, and the mixture was stirred at roomtemperature for minutes. Next, 52 μg (0.57 mmol) of(chloromethyl)cyclopropane and 5 mg of potassium iodide were added inthis order, and the mixture was stirred at room temperature for 20hours. Following reaction completion, the reaction was stopped by addinga small amount of water to the reaction mixture, and liquid-liquidextraction was carried out with 1% hydrochloric acid and ethyl acetate.The organic phase was washed with 1% hydrochloric acid, then dried overanhydrous magnesium sulfate, concentrated under reduced pressure, andpurified on a preparative TLC plate (one 0.5 mm plate; developed withhexane/ethyl acetate=1:1, giving 18 mg of the target compound (yield,45%).

Synthesis Example 12 2-[N-(6-Chloro-3-pyridylmethyl)cyanamide]ethylO-ethylcarbonodithioate (Compound 86)

1,2-bis(tosyloxy)ethane (8.86 g; 24.0 mmol) was dissolved in 100 mL ofanhydrous dimethylformamide, following which 2.00 g (12.0 mmol) ofN-[(6-chloropyridin-3-yl)methyl]cyanamide synthesized by the method in acomparative example, 500 mg of 60% NaH (net weight, 300 mg; 13.2 mmol)and 44 mg of KI were added in this order under ice cooling, and thesystem was stirred at room temperature for 80 minutes. Followingreaction completion, methanol was added a little at a time at 0° C.,then the reaction was stopped by adding water. Next, ethyl acetate and1% hydrochloric acid were added to the system and liquid-liquidextraction was carried out. The organic phase was washed with 1%hydrochloric acid, dried over anhydrous magnesium sulfate andconcentrated under reduced pressure, then purified by silica gel columnchromatography (hexane/ethyl acetate=2:8→6:4). When the fractionscontaining the target compound were collected and concentrated,dimethylformamide remained in the concentrate. Hence, a small amount ofethyl acetate was added and the concentrate was washed twice with 1%hydrochloric acid, then dried over anhydrous magnesium sulfate andconcentrated under reduced pressure to remove the dimethylformamide,giving 1.43 g of 2-[N-(6-chloro-3-pyridylmethyl)cyanamide]ethyl4-methylbenzenesulfonate (Compound 84). The yield was 33%.

Anhydrous acetonitrile (3 mL) was added to 45 mg (0.28 mmol) ofpotassium ethyl xanthate, a solution of 50 mg (0.14 mmol) of2-[N-(6-chloro-3-pyridylmethyl)cyanamide]ethyl 4-methylbenzenesulfonatesynthesized by the above-described method dissolved in 2 mL ofacetonitrile was added thereto, and the mixture was stirred at 50° C.for 50 minutes. Following reaction completion, the reaction mixture wasconcentrated under reduced pressure, ethyl acetate and 1% hydrochloricacid were added, and liquid-liquid extraction were carried out. Theorganic phase was dried over anhydrous magnesium sulfate, thenconcentrated under reduced pressure, purified on a preparative TLC plate(one 0.5 mm plate, liquid-liquid extraction with hexane/ethylacetate=2:3), giving 23 mg of the target compound (yield, 18%).

Synthesis Example 13 2-[N-(6-chloro-3-pyridylmethyl)cyanamide]ethylbenzyl(ethyl)carbamodithioate (Compound 85)

Benzyl ethyl amine (55 mg, 0.41 mmol) was dissolved in 5 mL of anhydroustetrahydrofuran, 46 mg (0.41 mmol) of potassium t-butylate was added,and the mixture was stirred at room temperature for 20 minutes. Next, 49μg (62 mg, 0.41 mmol) of carbon disulfide, 50 mg (0.14 mmol) of2-[N-(6-chloro-3-pyridylmethyl)cyanamide]ethyl 4-methylbenzenesulfonate(Compound 84) synthesized by the method of Synthesis Example 12dissolved in 3 mL of anhydrous tetrahydrofuran, and 5 mg of potassiumiodide were added in this order, and the system was stirred at 40° C.for 1 hour. Following reaction completion, a small amount of water wasadded to stop the reaction, the reaction mixture was filtered usingCelite, and the filtrate was concentrated. The concentrate was purifiedby silica gel column chromatography (hexane/ethyl acetate=7:3), giving41 mg of the target compound (yield, 72%).

Tables 6 to 9 below present spectral data on the compounds obtained inSynthesis Examples 1 to 13 and on other compounds obtained by similarmethods.

In the tables, the synthesis methods are referred to as follows.

A: Methods similar to those used in Synthesis Examples 1 to 5 and 10

B: Methods similar to those used in Synthesis Examples 6 and 7

C: Methods similar to that used in Synthesis Example 8

D: Methods similar to that used in Synthesis Example 9

E: Methods similar to that used in Synthesis Example 11

F: Methods similar to those used in Synthesis Examples 12 and 13

TABLE 6 Compound Synthesis No. Method ¹H-NMR (CDCl₃, δ, ppm) IR (KBr, v,cm⁻¹) or MS 1 A 2.40 (3H, s), 2.89 (2H, s), 3.35 (2H, s), 4.27 (2H, s),7.40 (1H, d), 7.75 (1H, dd), 2211 (CN) 8.36 (1H, d) 2 A 1.32 (3H, t),2.68 (2H, q), 2.87 (2H, t), 3.34 (2H, t), 4.27 (2H, s), 7.41 (1H, d),2211 (CN) 7.74 (1H, dd), 8.37 (1H, d) 3 A 0.99 (3H, t), 1.69 (2H, m),2.65 (2H, t), 2.86 (2H, t), 3.34 (2H, t), 4.27 (2H, s), 2211 (CN) 7.40(1H, d), 7.74 (1H, dd), 8.36 (1H, d) 4 A 0.97 (3H, t), 1.69 (2H, m),2.92 (2H, t), 4.19 (2H, s), 7.39 (1H, d), 7.71 (1H, dd), 2209 (CN) 8.33(1H, d) 5 A 1.96 (2H, m), 2.11 (3H, s), 2.58 (2H, t), 3.11 (2H, t), 4.21(2H, s), 7.39 (1H, d), 2210 (CN) 7.71 (1H, dd), 8.35 (1H, d) 6 E 2.76(3H, s), 3.31 (2H, t), 3.63 (2H, t), 4.28 (2H, s), 7.38 (1H, d), 7.73(1H, dd), 2211 (CN), m/z = 318 (M + H) 8.35 (1H, d) 7 E 1.36 (3H, t),3.30 (2H, t), 3.36 (2H, q), 3.61 (2H, t), 4.27 (2H, s), 7.39 (1H, d),m/z = 332 (M + H) 7.73 (1H, dd), 8.36 (1H, d) 8 E 1.02 (3H, t), 1.73(2H, m), 3.30 (2H, t), 3.34 (2H, t), 3.61 (2H, t), 4.27 (2H, s), m/z =346 (M + H) 7.38 (1H, s), 7.73 (1H, dd), 8.36 (1H, d) 9 E 1.37 (3H, t),2.33 (2H, t), 3.38 (2H, q), 4.42 (2H, s), 7.51 (1H, s) 2213 (CN), m/z =338 (M + H) 10 E 1.03 (3H, t), 1.75 (2H, q), 3.32 (2H, t), 3.36 (2H, t),3.62 (2H, t), 4.42 (2H, s), 2214 (CN), m/z = 352 (M + H) 7.51 (1H, s) 11A 3.19 (2H, t), 3.38 (3H, s), 3.61 (2H, t), 4.30 (2H, s), 7.38 (1H, d),7.72 (1H, dd), 2212 (CN) 8.35 (1H, d) 12 A 0.93 (3H, t), 1.39 (2H, m),1.65 (2H, m), 2.96 (2H, t), 4.19 (2H, s), 7.38 (1H, d), 2210 (CN) 7.71(1H, dd), 8.33 (1H, d) 13 A 2.83 (3H, s), 4.17 (2H, s), 7.41 (1H, d),7.71 (1H, dd), 8.34 (1H, d) 2208 (CN) 14 A 1.30 (3H, t), 3.03 (2H, q),4.20 (2H, s), 7.39 (1H, d), 7.71 (1H, dd), 8.34 (1H, d) 2210 (CN) 15 A1.29 (6H, d), 3.15 (1H, sept), 4.20 (2H, s), 7.39 (1H, d), 7.70 (1H,dd), 8.34 (1H, d) 2210 (CN) 16 A 2.23 (6H, s), 2.54 (2H, t), 3.06 (2H,t), 4.26 (2H, s), 7.37 (1H, d), 7.73 (1H, dd), 2211 (CN) 8.34 (1H, d) 17B 1.66 (1H, m), 1.82 (2H, m), 2.20 (1H, m), 3.03 (1H, m), 3.17 (1H, m),4.13 (1H, t), 2207 (CN) 7.22 (1H, m), 7.68 (1H, d), 8.45 (1H, d), 8.57(1H, s) 18 C 1.24 (3H, t), 1.65 (3H, d), 2.91 (2H, m), 4.13 (1H, q),7.36 (1H, d), 7.72 (1H, dd), 2206 (CN) 8.30 (1H, d) 19 A 1.28 (3H, t),3.03 (2H, q), 4.32 (2H, s), 7.47 (1H, s) 2213 (CN) 20 A 1.12, 1.17 (3H,t), 2.12, 2.17 (3H, s), 3.29, 3.41 (2H, q), 4.53, 4.55 (2H, s), 7.29,1635 (C═O) 7.35 (1H, d), 7.41, 7.63 (2H, dd), 8.27 (1H, d) 21 A 1.13,1.26 (3H, t), 3.36, 3.44 (2H, q), 4.60, 4.61 (2H, s), 7.31, 7.38 (1H,d), 7.54, 1691 (C═O) 7.61 (1H, dd), 8.28, 8.30 (1H, d) 22 A 1.10 (3H,m), 3.25 (2H, m), 3.74 (3H, m), 4.44 (2H, m), 7.29 (1H, m), 7.58 (1H,m), 1702 (C═O) 8.28 (1H, m) 24 A 2.12, 2.13 (3H, s), 2.14, 2.21 (3H, s),2.62, 2.67 (2H, t), 3.46, 3.54 (2H, t), 4.60, m/z = 259 (M + H) 4.63(2H, s), 7.30, 7.36 (1H, d), 7.51, 7.63 (1H, dd), 8.27 (1H, d) 25 A2.12, 2.13 (3H, s), 2.72 (3H, t), 3.57, 3.58 (3H, t), 4.58, 4.69 (2H,s), m/z = 337 (M + H) 7.07-7.43 (6H, m), 7.68 (1H, dd), 8.37 (1H, d) 26A 1.98 (3H, s), 2.44 (2H, t), 3.29 (2H, t), 4.37 (2H, s), 7.33 (1H, d),7.56 (2H, dd), m/z = 357 (M + H) 7.63 (1H, td), 7.74 (1H, dd), 7.84 (2H,dd), 8.23 (1H, d) 27 A 2.10 (3H, s), 2.63 (2H, m), 3.43 (2H, m), 3.76(3H, m), 4.52 (2H, s), 7.30 (1H, m), m/z = 275 (M + H) 7.60 (1H, m),8.30 (1H, m) 28 A 2.07 (3H, s), 2.58 (2H, t), 3.01 (3H, s), 3.38 (2H,t), 4.42 (2H, s), 7.36 (1H, d), m/z = 295 (M + H) 7.80 (1H, dd), 8.34(1H, d) 29 A 2.09, 2.10 (3H, s), 2.57, 2.61 (2H, t), 3.37, 3.42 (2H, t),4.52, 4.55 (2H, s), 7.32, m/z = 245 (M + H) 7.37 (1H, d), 7.56, 7.64(1H, dd), 8.31, 8.32 (1H, d) 30 A 1.80 (3H, m), 2.60 (2H, m), 3.50 (2H,m), 4.74 (2H, m), 7.32 (1H, d), 7.42 (5H, m), m/z = 321 (M + H) 7.53,7.68 (1H, dd), 8.16 (1H, d) 31 A 2.11, 2.13 (3H, s), 2.67 (2H, t), 3.50,3.58 (2H, t), 4.67, 4.74 (2H, s), 7.34, m/z = 313 (M + H) 7.38 (1H, d),7.55, 7.62 (1H, dd), 8.30, 8.32 (1H, d) 33 A 1.33 (6H, t), 2.06 (3H, s),2.56 (2H, t), 3.09 (2H, m), 4.08 (4H, m), 4.26 (2H, m), m/z = 353 (M +H) 7.32 (1H, d), 7.72 (1H, dd), 8.33 (1H, d) 34 A 2.13 (3H, s), 2.90(2H, t), 3.14 (2H, t), 4.19 (2H, s), 7.44 (1H, d), 8.17 (1H, dd), m/z =361 (M + H) 8.47 (1H, d) 35 A 1.26 (3H, t), 2.98 (2H, q), 4.19 (2H, s),7.35 (5H, m) m/z = 161 (M + H) 36 A 1.29 (3H, t), 3.02 (2H, q), 4.22(2H, s), 7.36 (1H, dd), 7.73 (1H, dd), 8.56 (1H, d), m/z = 162 (M + H)8.62 (1H, dd) 37 A 1.27 (3H, t), 3.00 (2H, q), 4.16 (2H, s), 7.27 (2H,d), 7.35 (2H, d) m/z = 195 (M + H) 39 A 1.12 (3H, t × 2), 2.11, 2.18(3H, s), 3.28, 3.43 (2H, t), 4.51, 4.59 (2H, s), 7.29 (5H, m) 40 A 1.07(3H, m), 3.25 (2H, m), 3.74 (3H, s), 4.47 (2H, s), 7.28 (5H, m) 41 A1.25 (3H, t), 2.99 (2H, q), 4.20 (2H, s), 7.11 (1H, m), 7.25 (1H, m),7.36 (1H, m) m/z = 167 (M + H) 42 A 2.54 (1H, t), 3.81 (2H, d), 4.30(2H, s), 7.40 (1H, d), 7.73 (1H, dd), 8.39 (1H, d) m/z = 206 (M + H) 43A 3.62 (2H, dd), 4.19 (2H, s), 5.37 (2H, dd × 2), 5.85 (1H, tdd), 7.39(1H, d), 7.71 (1H, m/z = 208 (M + H) dd), 8.33 (1H, d) 44 A 4.10 (2H,s), 4.17 (2H, s), 7.33 (6H, m), 7.65 (1H, dd), 8.23 (1H, d) m/z = 258(M + H) 45 A 1.32 (3H, t), 3.03 (2H, q), 4.23 (2H, s), 7.53 (1H, m),7.64 (3H, m) m/z = 186 (M + H) 46 A 1.32 (3H, t), 3.06 (2H, q), 4.31(2H, s), 7.75 (1H, d), 7.93 (1H, dd), 8.68 (1H, d) m/z = 230 (M + H) 47A 2.14 (3H, s), 2.78 (2H, t), 3.25 (2H, t), 4.38 (2H, s), 7.76 (1H, d),7.97 (1H, dd), m/z = 276 (M + H) 8.72 (1H, d)

TABLE 7 Compound Synthesis No. Method ¹H-NMR (CDCl₃, δ, ppm) IR (KBr, v,cm⁻¹) or MS 48 A 1.26 (3H, t), 2.56 (2H, m), 2.81 (2H, q), 3.24 (2H, t),4.38 (2H, s), 7.75 (1H, d), m/z = 290 (M + H) 7.96 (1H, d), 8.71 (1H, s)49 A 2.75 (2H, t), 3.05 (2H, t), 3.73 (2H, s), 4.20 (2H, s), 6.18 (1H,d), 6.31 (1H, dd), m/z = 308 (M + H) 7.35 (1H, d), 7.38 (1H, d), 7.71(1H, dd), 8.31 (1H, d) 50 A 2.65 (2H, t), 2.99 (2H, t), 3.72 (2H, s),4.11 (2H, s), 7.30 (6H, m), 7.64 (1H, dd), m/z = 318 (M + H) 8.26 (1H,d) 51 A 3.44 (2H, m), 3.48 (2H, m), 4.23 (2H, s), 7.37 (1H, d), 7.61(2H, m), 7.70 (2H, m), m/z = 336 (M + H) 7.91 (2H, m), 8.33 (1H, d) 52 A3.12 (2H, td), 3.17 (2H, td), 4.18 (2H, s), 7.31 (6H, m), 7.68 (1H, dd),8.25 (1H, m) m/z = 304 (M + H) 53 A 3.43 (2H, t), 4.19 (2H, t), 4.35(2H, s), 6.88 (2H, d), 7.02 (1H, m), 7.31 (3H, m), m/z = 288 (M + H)7.72 (1H, dd), 8.36 (1H, d) 54 A 2.01 (3H, s), 3.17 (2H, t), 3.50 (2H,q), 4.24 (2H, s), 5.92 (1H, brs), 7.39 (1H, d), m/z = 253 (M + H) 7.69(1H, dd), 8.36 (1H, d) 55 B 4.08 (4H, s), 7.23 (4H, d), 7.36 (4H, d) m/z= 291 (M + H) 57 E 2.96 (2H, t), 3.20 (2H, t), 4.07 (2H, s), 7.17 (2H,m), 7.29 (4H, m), 7.48 (1H, dd), m/z = 272 (M + H) 8.18 (1H, d) 58 E3.43 (2H, t), 4.98 (2H, s), 4.53 (2H, t), 7.33 (1H, d), 7.47 (1H, m),7.60 (1H, m), m/z = 316 (M + H) 7.71 (1H, dd), 8.03 (2H, m), 8.35 (1H,d) 59 E 3.98 (2H, s), 4.36 (2H, s), 7.45 (1H, d), 7.74 (1H, dd), 8.42(1H, d) m/z = 207 (M + H) 61 E 2.11 (3H, s), 3.28 (2H, t), 4.27 (4H, m),7.40 (1H, d), 7.71 (1H, dd), 8.36 (1H, d) m/z = 254 (M + H) 62 E 2.25(3H, s), 4.17 (2H, s), 4.33 (2H, s), 7.39 (1H, d), 7.72 (1H, dd), 8.37(1H, d) m/z = 228 (M + H) 68 E 2.21 (1H, dd), 2.58 (1H, dd), 3.08 (2H,m), 3.32 (1H, dd), 4.31 (2H, dd), 7.39 (1H, d), 7.72 (1H, dd), 8.36 (1H,d) 69 E 2.60 (1H, dd), 2.88 (2H, m), 3.21 (1H, m), 3.49 (1H, dd), 4.31(2H, s), 7.38 (1H, d), 7.74 (1H, dd), 8.39 (1H, d) 70 E 2.70 (2H, t),3.30 (2H, t), 3.73 (3H, s), 4.25 (2H, s), 7.38 (1H, d), 7.72 (1H, dd),8.35 (1H, d) 71 E 0.27 (2H, m), 0/66 (2H, m), 1.06 (1H, m), 2.88 (2H,d), 4.26 (2H, s), 7.40 (1H, d), m/z = 222 (M + H) 7.75 (1H, dd), 8.34(1H, d) 72 A 2.14 (3H, s), 2.77 (2H, t), 3.23 (2H, t), 4.28 (2H, s),7.87 (1H, d), 8.28 (1H, d) m/z = 276 (M + H) 73 C 1.69 (3H, d), 2.90(3H, s), 2.77 (2H, m), 3.08 (2H, m), 4.23 (1H, q), 7.38 (1H, d), m/z =256 (M + H) 7.76 (1H, dd), 8.33 (1H, d) 74 A 2.15 (3H, s), 2.75 (2H, t),3.23 (2H, t), 4.24 (2H, s), 7.51 (1H, s) m/z = 248 (M + H) 75 A 1.27(3H, t), 2.58 (2H, q), 2.78 (2H, t), 3.21 (2H, t), 4.42 (2H, s), 7.51(1H, s) m/z = 262 (M + H) 76 A 2.22 (2H, m), 2.92 (4H, m), 3.63 (1H, m),4.26 (2H, s), 7.39 (1H, d), 7.73 (1H, dd), m/z = 254 (M + H) 8.36 (1H,d), 77 A 1.36 (3H, d), 2.11 (3H, d), 2.62 (1H, dd), 2.79 (1H, dd), 3.15(1H, m), 4.29 (1H, d), m/z = 256 (M + H) 4.32 (1H, d), 7.38 (1H, d),7.76 (1H, dd), 8.37 (1H, d) 78 A 2.11 (3H, s), 2.75 (2H, t), 3.21 (2H,t), 4.27 (2H, s), 7.00 (1H, dd), 7.89 (1H, td), m/z = 226 (M + H) 8.19(1H, d) 79 A 2.14 (3H, s), 2.78 (2H, t), 3.23 (2H, t), 4.30 (2H, s),7.59 (1H, dd), 8.21 (1H, s) m/z = 260 (M + H) 80 A 1.30 (3H, t), 3.01(2H, q), 4.21 (2H, s), 7.54 (1H, d), 8.19 (1H, s) m/z = 214 (M + H) 81 A3.60, 3.68, 3.70 (2H, dt × 2), 4.60, 4.69 (2H, t × 2), 4.77, 4.78 (2H, s× 2), 7.33, 7.39 (1H, m/z = 285 (M + H) d × 2), 7.55, 7.63 (1H, dd × 2),8.30, 8.33 (1H, d × 2) 82 A 3.30 (2H, dt), 4.31 (2H, s), 4.31-4.73 (2H,m), 7.39 (1H, d), 7.73 (1H, dd), 8.36 (1H, m/z = 214 (M + H) d) 83 E4.18 (2H, s), 4.32 (2H, s), 7.40 (1H, d), 7.48 (1H, s) 7.69 (1H, dd),8.33 (1H, d) m/z = 299 (M + H) 84 E 2.47 (3H, s), 3.31 (2H, t), 4.21(2H, t), 4.23 (2H, s), 7.37 (3H, m), 7.68 (1H, dd), m/z = 366 (M + H)7.79 (2H, d), 8.30 (1H, d) 85 F 1.22 (3H, t × 2), 3.36 (2H, t × 2), 3.60(2H, t × 2), 3.71 (2H, q), 4.02 (2H, q), 4.28, m/z = 405 (M + H) 4.32(2H, s × 2), 4.94, 5.31 (2H, s × 2), 7.32 (6H, m), 7.74 (1H, m), 8.38(1H, m) 86 F 1.42 (3H, t), 3.31 (2H, t), 3.38 (2H, t), 4.28 (2H, s),4.63 (2H, q), 7.38 (1H, d), m/z = 316 (M + H) 7.72 (1H, dd), 8.37 (1H,d) 88 F 3.25, 3.47 (3H, s × 2), 3.36 (2H, t × 2), 3.60 (2H, t × 2),4.29, 4.32 (2H, s × 2), 4.98, m/z = 391 (M + H) 5.33 (2H, s × 2),7.18-7.37 (6H, m), 7.73 (2H, m), 8.41 (1H, m) 89 C 1.74 (3H, m), 3.19(1H, m), 3.37-3.82 (1H, m), 4.31-4.66 (2H, m), 5.33 (1H, m), m/z = 299(M + H) 7.37 (1H, d × 2), 7.57, 7.70 (1H, dd × 2), 8.35, 8.38 (1H, d ×2) 90 F 1.39 (6H, d), 3.30-3.40 (4H, m), 5.73 (1H, m), 7.38 (1H, d),7.73 (1H, dd), 8.37 (1H, d) m/z = 330 (M + H) 91 F 0.92 (3H, t), 1.37(4H, m), 1.79 (2H, m), 3.31 (2H, t), 3.38 (2H, t), 4.29 (2H, s), m/z =358 (M + H) 4.57 (2H, t), 7.38 (1H, d), 7.73 (1H, dd), 8.37 (1H, d) 92 C1.70 (3H, d), 3.22 (2H, m), 4.29 (1H, q), 4.64 (2H, m), 7.39 (1H, d),7.74 (1H, dd), m/z = 228 (M + H) 8.33 (1H, d) 93 F 1.00 (3H, t), 1.38(2H, m), 3.31 (2H, t), 3.38 (2H, t), 4.29 (2H, s), 4.53 (2H, t), m/z =330 (M + H) 7.38 (1H, d), 7.73 (1H, dd), 8.37 (1H, d) 94 F 0.96 (3H, t),1.41 (2H, m), 1.80 (2H, m), 3.31 (2H, t), 3.38 (2H, t), 4.28 (2H, s),m/z = 344 (M + H) 4.58 (2H, t), 7.38 (1H, d), 7.73 (1H, dd), 8.36 (1H,d) 95 A 3.68, 3.76 (2H, td × 2), 4.78, 4.88 (2H, s × 2), 5.85-6.15 (1H,m), 7.52, 7.56 (1H, s × 2) m/z = 309 (M + H) 96 C 1.73 (3H, d), 3.16,3.49 (2H, m × 2), 5.27, 5.37 (1H, q × 2), 7.33, 7.40 (1H, d × 2), 7.56,m/z = 317 (M + H) 7.70 (1H, d × 2), 8.36 (1H, d) 97 A 3.60, 3.71 (2H, td× 2), 4.79 (2H, s), 5.85-6.18 (1H, m), 7.36, 7.40 (1H, d × 2), 7.53, m/z= 303 (M + H) 7.60 (1H, dd × 2), 8.30, 8.36 (1H, d × 2)

TABLE 8 Compound Synthesis IR (KBr, v, No. Method ¹H-NMR (CDCl₃, δ, ppm)cm⁻¹) or MS 98 F 3.59, 3.87 (2H, td × 2), 4.76, 4.85 (2H, s × 2),5.86-6.17 (1H, m), 7.37, 7.41 (1H, d × 2), 7.55, m/z = 319 (M + H) 7.62(1H, d × 2), 8.31, 8.32 (1H, s × 2) 99 A 3.59 (2H, m), 5.11 (2H, m),6.10 (1H, m), 7.37 (1H, d), 7.60 (1H, d), 8.32 (1H, s) m/z = 351 (M + H)100 F 2.03 (2H, m), 2.47 (3H, s), 3.09 (2H, t), 4.12 (2H, t), 4.18 (2H,s), 7.38 (3H, m), 7.70 (1H, m/z = 380 (M + H) dd), 7.78 (1H, d), 8.33(1H, d) 101 F 1.43 (3H, t), 2.10 (2H, m), 3.10 (2H, t), 3.20 (2H, t),4.21 (2H, s), 4.66 (2H, q), 7.39 (1H, d), m/z = 330 (M + H) 7.71 (1H,dd), 8.34 (1H, d) 102 F 1.00 (2H, t), 1.83 (2H, q), 2.11 (2H, q), 3.09(2H, t), 3.19 (2H, t), 4.21 (2H, s), 4.55 (2H, t), m/z = 344 (M + H)7.38 (1H, d), 7.71 (1H, dd), 8.34 (1H, d) 103 F 1.25 (3H, m), 2.12 (2H,m), 3.06, 3.12 (2H, t × 2), 3.36, 3.40 (2H, t × 2), 3.71, 4.05 (2H, q ×2), m/z = 419 (M + H) 4.19, 4.23 (2H, s × 2), 4.94, 5.33 (2H, s × 2),7.33 (7H, m), 7.72 (1H, m), 8.33 (1H, m) 104 A 3.58 (2H, m), 4.67 (2H,m), 5.77-6.07 (1H, m), 7.41 (1H, d), 7.72 (1H, dd), 8.37 (1H, d) 105 C1.01, 1.17 (3H, t × 2), 1.72 (3H, d × 2), 3.02-3.54 (2H, m), 5.28, 5.38(1H, q × 2), 7.34, 7.38 m/z = 281 (M + H) (1H, d × 2), 7.57, 7.66 (1H,dd × 2), 8.37 (1H, m) 107 C 1.02 (3H, t), 1.72 (3H, d), 3.28 (2H, m),5.26 (1H, q), 7.37 (1H, d), 7.77 (1H, d), 8.44 (1H, d) m/z = 317 (M + H)108 C 1.70, 1.75 (3H, d × 2), 3.16-3.58 (2H, m), 5.30 (1H, q), 5.61-5.96(1H, m), 7.38, 7.41 (1H, d × 2), m/z = 353 (M + H) 7.73 (1H, dd), 8.41,8.44 (1H, d × 2) 109 C 1.01 (3H, m), 2.03, 2.24 (2H, m × 2), 3.32, 3.72(2H, m × 2), 5.03 (1H, q), 5.60-6.20 (1H, m), 7.37, m/z = 331 (M + H)7.41 (1H, d × 2), 7.60, 7.76 (1H, dd × 2), 8.39 (1H, d) 110 C 0.97 (3H,t), 2.04-2.32 (2H, m), 3.30-3.60 (2H, m), 5.72-6.00 (1H, m), 7.41 (1H,d), 7.72 (1H, m/z = 367 (M + H) m), 8.44 (1H, s) 111 C 1.02 (3H, m),2.00-2.30 (2H, m), 3.14-3.38 (2H, m), 4.94-5.12 (1H, m), 7.26-7.34 (1H,m), m/z = 295 (M + H) 7.60-7.76 (1H, m), 8.38 (1H, m) 112 C 0.98, 1.05(3H, t), 2.06, 2.24 (2H, m × 2), 3.32 (2H, m), 4.90 (1H, q), 7.38 (1H,d), 7.75 (1H, m), m/z = 331 (M + H) 8.45 (1H, s) 114 C 1.03 (3H, t),1.78 (3H, d), 3.20-3.45 (2H, m), 5.32 (1H, q), 7.73 (1H, d), 7.98 (1H,d), m/z = 351 (M + H) 8.82 (1H, s) 115 C 1.03, 1.23 (3H, t × 2), 1.78(3H, d × 2), 3.00-3.60 (2H, m), 5.34 (1H, q), 7.69. 7.73 (1H, d × 2),m/z = 315 (M + H) 7.80. 7.88 (1H, d × 2), 8.70, 8.71 (1H, d × 2) 119 E3.63 (2H, d), 4.33 (2H, s), 5.38 (2H, m), 5.83 (1H, m), 7.47 (1H, s) m/z= 214 (M + H) 120 E 2.55 (1H, t), 3.83 (2H, d), 4.46 (2H, s), 7.55 (1H,s) m/z = 212 (M + H) 121 E 2.86 (3H, s), 4.31 (2H, s), 7.50 (1H, s) m/z= 188 (M + H) 122 E 0.98 (3H, t), 1.69 (2H, m), 2.95 (2H, t), 4.33 (2H,s), 7.49 (1H, s) m/z = 216 (M + H) 124 C 0.95 (3H, m), 1.73 (3H, d),3.47 (2H, m), 5.22 (1H, m), 7.25 (2H, m), 7.71 (1H, td), 8.58 (1H, d)m/z = 283 (M + H) 128 A 2.50 (1H, t), 4.23 (2H, m), 4.71 (2H, m), 7.41(1H, d), 7.75 (1H, dd), 8.41 (1H, d) m/z = 313 (M + H) 129 A 3.96 (2H,m), 4.55 (2H, m), 7.44 (1H, d), 7.74 (1H, dd), 8.44 (1H, d) m/z = 314(M + H) 130 A 1.23 (3H, t × 2), 3.49 (2H, q × 2), 4.86 (2H, s × 2), 7.56(1H, d × 2), 8.58 (1H, s × 2), 8.74 (1H, d × 2) m/z = 301 (M + H) 131 A1.20 (3H, t), 3.42 (2H, m), 4.64 (2H, m), 7.74 (1H, d), 7.96 (1H, dd),8.70 (1H, d) m/z = 337 (M + H) 132 C 1.04, 1.16, 1.31 (3H, t × 3), 1.70(3H, d × 2), 2.90-3.58 (2H, m), 5.25, 5.40 (1H, q × 2), 7.22, m/z = 247(M + H) 7.34 (2H, d × 2), 8.60, 8.65 (2H, d × 2) 133 C 0.97, 1.10 (3H, t× 2), 1.73 (3H, d), 3.07-3.52 (2H, m), 5.32, 5.52 (1H, q × 2), 7.34 (1H,m), 7.62, m/z = 247 (M + H) 7.70 (1H, d × 2), 8.56, 8.60 (1H, d × 2) 134C 0.92, 1.08 (3H, t × 2), 1.71 (3H, d), 3.18-3.58 (2H, m), 5.28, 5.53(1H, q × 2), 7.20-7.36 (2H, m), m/z = 247 (M + H) 7.69 (1H, m), 8.57,8.62 (1H, d × 2) 135 A 2.94 (3H, s), 4.52 (2H, m), 7.39 (1H, d), 7.71(1H, dd), 8.34 (1H, d) m/z = 289 (M + H) 136 E 2.47 (3H, s), 3.33 (2H,t), 4.22 (2H, t), 4.39 (2H, s), 7.38 (2H, d), 7.48 (1H, s), 7.81 (2H, d)m/z = 372 (M + H) 137 F 1.43 (3H, t), 3.37 (4H, m), 4.43 (2H, s), 4.67(2H, q), 7.51 (1H, s) m/z = 322 (M + H) 138 F 1.26 (3H, t), 3.40 (2H, t× 2), 3.60 (2H, t × 2), 3.74, 4.06 (2H, q × 2), 4.43, 4.48 (2H, s × 2),4.95, m/z = 411.0286 5.30 (2H, s × 2), 7.20-7.40 (5H, m), 7.53, 7.56(1H, s × 2) (M + H) 139 A 2.70 (3H, s), 2.97 (1H, m), 3.10 (1H, m), 3.51(2H, m), 4.31 (2H, dd), 7.40 (1H, d), 7.76 (1H, m/z = 258 (M + H) dd),8.40 (1H, d) 140 A 1.53 (6H, d), 4.24 (1H, m), 4.54 (2H, m), 7.35 (1H,d), 7.81 (1H, dd), 8.37 (1H, d) m/z = 317 (M + H) 141 A 0.83 (3H, t),1.22 (2H, m), 1.55 (2H, m), 3.28 (2H, m), 4.61 (2H, m), 7.40 (1H, d),7.74 (1H, m/z = 331 (M + H) dd), 8.34 (1H, d) 142 A 3.23 (2H, m), 3.70(2H, m), 4.60 (2H, m), 7.24 (2H, m), 7.24-7.83 (7H, m), 8.32 (1H, d) m/z= 443 (M + H) 143 A 3.70 (2H, m), 4.11 (2H, m), 4.74 (2H, m), 6.81 (2H,m), 7.26 (1H, d), 7.34 (3H, m), 7.75 (1H, d), m/z = 395 (M + H) 8.41(1H, s) 144 A 1.16 (3H, t), 3.39 (2H, m), 4.74 (2H, m), 7.39 (1H, d),7.75 (1H, dd), 8.35 (1H, d) m/z = 303 (M + H) 145 A 0.84 (3H, t), 1.53(2H, m), 3.25 (2H, t), 4.55 (2H, m), 7.37 (1H, d), 7.76 (1H, dd), 8.32(1H, d) m/z = 317 (M + H) 146 A 3.99 (2H, m), 4.72 (2H, m), 5.22 (1H,dd), 5.36 (1H, dd), 5.71 (1H, m), 7.39 (1H, d), 7.72 (1H, m/z = 315 (M +H) dd), 8.29 (1H, d) 147 A 4.44 (4H, m), 7.18 (2H, m), 7.25 (1H, d),7.33 (2H, m), 7.53 (1H, dd), 8.03 (1H, d) m/z = 365 (M + H) 148 A 1.30(3H, t), 3.05 (2H, q), 4.21 (2H, s), 7.00 (1H, dd), 7.86 (1H, td), 8.18(1H, d) m/z = 180 (M + H) 149 A 1.29 (3H, t), 3.02 (2H, q), 4.18 (2H,s), 7.53 (1H, d), 7.61 (1H, dd), 8.32 (1H, d) m/z = 240 (M + H)

TABLE 9 Compound Synthesis No. Method ¹H-NMR (CDCl₃, δ, ppm) IR (KBr, v,cm⁻¹) or MS 150 A 2.15 (6H, s), 3.36 (2H, t), 4.60 (4H, m), 7.38 (1H,d), 7.76 (1H, dd), 8.36 (1H, d) m/z = 346 (M + H) 151 A 1.04 (3H, t),3.37 (2H, q), 4.52 (2H, s), 7.37 (1H, d), 7.80 (1H, dd), 8.32 (1H, d)m/z = 401 (M + H) 152 A 2.07 (1H, t), 2.43 (2H, m), 3.48 (2H, t),, 4.69(2H, m), 7.40 (1H, d), 7.76 (1H, dd), 8.36 (1H, d) m/z = 327 (M + H) 153A 1.32 (3H, t), 3.06 (2H, q), 4.21 (2H, s), 7.23 (1H, dd), 7.31 (1H, d),8.42 (1H, d) m/z = 196 (M + H) 154 A 1.30 (3H, t), 3.14 (2H, q), 4.31(2H, s), 7.30 (1H, d), 7.38 (1H, d), 7.72 (1H, dd) m/z = 196 (M + H) 155A 3.29 (3H, s), 3.45 (4H, m), 4.68 (2H, m), 7.36 (1H, d), 7.74 (1H, dd),8.37 (1H, d) m/z = 333 (M + H) 157 A 1.17, 1.31 (3H, t × 2), 3.48, 3.63(2H, q × 2), 7.52 (1H, d), 7.60 (1H, d) m/z = 268 (M + H) 158 A 1.30(3H, t), 3.01 (2H, q), 4.13 (2H, s), 7.23 (2H, s), 7.35 (1H, s) m/z =229 (M + H) 159 A 2.58 (2H, m), 3.61 (2H, t), 4.52 (2H, m), 7.43 (1H,d), 7.78 (1H, dd), 8.41 (1H, d) m/z = 328 (M + H) 160 A 3.75 (3H, s),3.94 (2H, m), 4.71 (2H, m), 7.39 (1H, d), 7.72 (1H, dd), 8.29 (1H, d)m/z = 347 (M + H) 161 A 4.03 (2H, m), 4.74 (2H, m), 7.40 (1H, d), 7.73(1H, dd), 8.31 (1H, d) m/z = 333 (M + H) 163 A 4.26 (2H, m), 4.82 (2H,m), 7.63 (1H, s) m/z = 320 (M + H) 165 A 4.02 (2H, m), 4.84 (2H, m),7.79 (1H, d), 8.00 (1H, dd), 8.78 (1H, d) m/z = 348 (M + H) 167 A 4.20(2H, m), 4.64 (2H, m), 7.58 (1H, dd), 8.27 (1H, d) m/z = 332 (M + H) 170C 1.90 (3H, d), 3.83 (1H, d), 4.27 (1H, d), 5.42 (1H, q), 7.43 (1H, d),7.76 (1H, dd), 8.47 (1H, d) m/z = 328 (M + H) 171 C 1.86 (3H, d), 2.28(1H, t), 3.78 (1H, d), 4.17 (1H, d), 5.34 (1H, q), 7.37 (1H, d), 7.78(1H, d), m/z = 327 (M + H) 8.47 (1H, d) 172 A 2.51 (1H, t), 4.25 (2H,m), 4.81 (2H, m), 7.56 (1H, s) m/z = 319 (M + H) 176 A 1.62 (3H, t),3.40 (2H, m), 4.03 (2H, m), 7.24 (2H, d), 7.36 (1H, d) m/z = 335 (M) 177A 1.12 (3H, t), 3.36 (2H, m), 4.57 (2H, m), 7.38 (5H, m) 178 A 1.10 (3H,m), 3.31 (2H, m), 3.81 (2H, m), 4.43 (2H, s), 7.38 (1H, d), 7.78 (1H,dd), 8.33 (1H, d) m/z = 317 (M + H) 179 A 2.51 (1H, t), 3.97 (4H, m),4.52 (2H, s), 7.37 (1H, d), 7.75 (1H, dd), 8.37 (1H, d) m/z = 327 (M +H) 180 A 1.14 (3H, t), 3.39 (2H, m), 4.50 (2H, m), 7.26 (2H, m), 7.34(3H, m) m/z = 301 (M) 181 A 1.12 (3H, t), 3.36 (2H, m), 4.60 (2H, m),7.30 (2H, d), 7.36 (2H, d) m/z = 301 (M) 182 A 1.15 (3H, t), 3.39 (2H,m), 4.50 (2H, m), 7.54 (1H, m), 7.67 (3H, m) m/z = 292 (M) 183 A 1.16(2H, t), 3.42 (2H, m), 4.50 (2H, m), 7.54 (2H, d), 8.27 (2H, d) m/z =312 (M) 184 A 2.50 (1H, t), 4.00 (2H, m), 4.65 (2H, m), 7.27 (2H, m),7.38 (1H, m) m/z = 345 (M) 185 A 1.11 (3H, t), 2.36 (3H, t), 3.34 (2H,m), 4.49 (2H, m), 7.20 (2H, d), 7.24 (2H, d) m/z = 281 (M) 186 A 1.14(3H, t), 3.39 (2H, m), 4.62 (2H, m), 7.48 (2H, d), 7.69 (2H, d) m/z =292 (M) 187 A 1.11 (3H, t), 3.34 (2H, m), 3.82 (3H, s), 4.40 (2H, m),6.88 (2H, d), 7.26 (2H, d) m/z = 297 (M) 188 A 1.12 (3H, t), 3.36 (2H,m), 4.51 (2H, m), 7.07 (2H, m), 7.33 (2H, m) m/z = 285 (M) 189 A 1.16(3H, t), 3.40 (2H, m), 4.50 (2H, m), 7.43 (2H, d), 7.66 (1H, d) 190 A1.12 (3H, t), 3.36 (2H, m), 4.56 (2H, m), 7.24 (2H, d), 7.52 (2H, d) m/z= 345 (M) 191 A 1.12 (3H, t), 2.32 (6H, s), 3.36 (2H, m), 4.51 (2H, m),6.94 (2H, s), 6.97 (1H, s) m/z = 295 (M) 192 A 1.17 (3H, t), 3.42 (2H,m), 4.63 (2H, m), 7.62 (1H, m), 7.75 (1H, d), 8.20 (1H, s), 8.22 (1H, d)m/z = 312 (M) 193 A 1.17 (3H, t), 3.43 (2H, m), 4.62 (2H, m), 7.37 (1H,d), 7.52 (1H, dd), 7.74 (1H, d) m/z = 423 (M) 194 A 1.92 (3H, t), 3.45(2H, m), 4.60 (2H, m), 7.87 (1H, s), 8.14 (1H, s), 8.38 (1H, s) m/z =390 (M) 195 A 1.19 (3H, t), 3.43 (2H, m), 4.68 (2H, m), 7.81 (2H, s),7.89 (1H, s) m/z = 403 (M) 196 E 3.32 (2H, t), 3.63 (2H, t), 3.76 (3H,s), 4.19 (2H, s), 4.27 (2H, s), 7.39 (1H, d), 7.73 (1H, dd), 1740 (C═O),2212 (CN) 8.35 (1H,d) 198 E 3.32 (2H, t), 3.40 (3H, s), 3.63 (2H, t),4.28 (2H, s) 5.46 (2H, s), 7.39 (1H, d), 7.73 (1H, dd), 2212 (CN) 8.36(1H, d) 199 E 2.22 (3H, s), 3.31 (2H, t), 3.63 (2H, t), 4.27 (2H, s),4.46 (2H, s), 7.39 (1H, d), 7.73 (1H, dd), 2212 (CN) 8.36 (1H, d) 200 E2.44 (3H, s), 3.31 (2H, t), 3.62 (2H, t), 4.26 (2H, s), 4.89 (2H, s),7.30 (2H, d), 7.39 (1H, d), 1684 (C═O), 2211 (CN) 7.72 (1H, dd), 7.90(2H, d), 8.34 (1H, d) 201 A 1.29 (3H, t), 1.63 (1H, m), 2.13 (1H, m),2.63 (1H, m), 2.99 (2H, m), 3.08 (2H, m), 3.57 (1H, m), 2209 (CN) 3.76(1H, q), 3.87 (2H, m) 202 A 1.64 (1H, m), 2.15 (4H, m), 2.75 (2H, t),3.04 (2H, m), 3.24 (2H, t), 3.69 (1H, dd), 3.76 (1H, q), 2207 (CN) 3.86(2H, m) 203 A 1.12 (3H, m), 3.25 (2H, m), 4.56 (2H, m), 7.32 (1H, d),7.75 (1H, m), 8.37 (1H, m) 1632, 1458, 1388 204 A 1.16, 1.24 (3H, t ×2), 3.31, 3.45 (2H, q × 2), 4.58, 4.66 (2H, s × 2), 6.16 (2H, td), 7.31,7.36 (1H, d × 2), 7.56, 7.61 (1H, dd × 2), 8.30 (1H, d) 205 A 1.14 (3H,t), 3.23 (2H, q), 4.48 (2H, s), 5.08 (2Hm brs), 7.29 (1H, d), 7.62 (1H,dd), 8.27 (1H, s) 206 A 1.13 (3H, t), 2.83 (3H, s), 3.20 (2H, q), 4.44(1H, brs), 4.49 (2H, s), 7.27 (1H, d), 7.64 (1H, dd), 8.27 (1H, s) 207 A1.14 (3H, t), 2.84 (6H, s), 3.14 (2H, m), 4.29 (2H, s), 7.25 (1H, d),7.63 (1H, d), 8.30 (1H, s) 208 A 1.19 (3H, t), 3.85 (2H, q), 5.06 (2H,s), 7.35 (1H, d), 7.73 (1H, dd), 8.27 (1H, d) m/z = 216 (M; H) 211 C1.70 (3H, d), 2.81 (3H, s), 5.33 (1H, q), 7.38 (1H, d), 7.71 (1H, dd),8.41 (1H, d) 1463, 1380, 1237

Synthesis Example 14N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamide(Compound 212)

(1) 2-aminopyridine in an amount of 25 g (270 mmol) was dissolved in 200mL of anhydrous dichloromethane, 41 mL (30 g, 300 mmol) of triethylaminewas added, and the mixture was cooled to 0° C. Next, 38 mL (57 g, 270mmol) of trifluoroacetic anhydride was added dropwise over 15 minutes,and the mixture was stirred at room temperature for 2 hours. Followingreaction completion, the reaction mixture was poured into about 100 mLof ice water and stirred for 10 minutes. The mixture was thentransferred to a separatory funnel and liquid-liquid extraction wascarried out. The organic phase was washed twice with 150 mL of water,washed twice with 150 mL of a 1% aqueous HCl solution, then dried overanhydrous magnesium sulfate and concentrated under reduced pressure,giving 36 g of 2,2,2-trifluoro-N-(pyridin-2(1H)-ylidene)acetamide(yield, 71%).

¹H-NMR (CDCl₃, δ, ppm): 7.20 (1H, ddd), 7.83 (1H, td), 8.20 (1H, d),8.35 (1H, d), 10.07 (1H, brs)

¹³C-NMR (CDCl₃, δ, ppm): 115.3, 115.5 (q), 121.6, 139.1, 147.9, 149.5,155.3 (q)

MS: m/z=191 (M+H)

(2) 2-chloro-5-chloromethylpyridine in an amount of 20 g (126 mmol) wasdissolved in 200 mL of anhydrous acetonitrile, then 24 g (126 mmol) of2,2,2-trifluoro-N-(pyridin-2(1H)-ylidene)acetamide obtained by the abovemethod and 21 g (151 mmol) of potassium carbonate were added andrefluxing under heating was carried out for 6 hours, followed by 10hours of stirring at room temperature. Following reaction completion,the reaction mixture was filtered, and the filtrate was concentratedunder reduced pressure. Diethyl ether was added to the concentrate toeffect crystallization, and the resulting crystals were collected byfiltration, then thoroughly washed with diethyl ether and water. Thecrystals thus obtained were dried at 60° C. and reduced pressure for 1hour, giving 26 g of the target compound (yield, 66%).

¹H-NMR (CDCl₃, δ, ppm): 5.57 (2H, s), 6.92 (1H, td), 7.31 (1H, d), 7.80(1H, td), 7.87 (1H, dd), 7.99 (1H, dd), 8.48 (2H, m)

¹³C-NMR (CDCl₃, δ, ppm): 53.8, 115.5, 117.2 (q), 122.1, 124.7, 130.0,139.2, 140.0, 142.5, 149.7, 151.8, 158.9, 163.5 (q)

MS: m/z=316 (M+H)

(3) Powder X-Ray Diffraction Analysis of Crystals

In powder x-ray diffraction analysis, measurement was carried out underthe following conditions.

Apparatus: RINT-2200 (Rigaku Corporation)

X-rays: Cu-Kα (40 kV, 20 mA)

Scanning range: 4 to 40°

Sampling width: 0.02°

Scanning rate: 1°/min

The results are given below (FIG. 1).

Diffraction angles (2θ): 8.7°, 14.2°, 17.5°, 18.3°, 19.8°, 22.4°, 30.9°,35.3°

(4) Differential Scanning Calorimetry (DSC)

In differential scanning calorimetry, measurement was carried out underthe following conditions.

Apparatus: DSC-60

Sample cell: aluminum

Temperature range: 50 to 250° C. (temperature rise rate, 10° C./min)

The results are shown in FIG. 2.

(5) In addition, similar crystals were obtained by using the methodsdescribed in (i) to (iv) below (second to fifth preparation methods) tocarry out recrystallization. The resulting crystals were subjected topowder x-ray diffraction analysis and differential scanning calorimetryunder the same measurement conditions as indicated above.(i) Second Preparation Method

About 25 mL of hexane and about 25 mL of ethyl acetate were added toCompound 212 (700 mg) and the mixture was heated to 65° C. on a hotwater bath, effecting complete dissolution. The solution was slowlyreturned to room temperature and left to stand overnight. The crystalsthat precipitated out were collected by filtration and washed with asmall amount of a 95:5 solution of hexane and ethyl acetate. The washedcrystals were placed in a desiccator and dried for 2 hours under reducedpressure, giving 349 mg of white crystals.

The results of powder x-ray diffraction analysis were as follows (FIG.3).

Diffraction angle (2θ): 8.5°, 14.0°, 17.3°, 18.1°, 19.6°, 22.2°, 30.8°,35.2°

The results of differential scanning analysis are shown in FIG. 4.

(ii) Third Preparation Method

An amount of 28 mL of 2-propanol was added to Compound 212 (1.0 g) andthe mixture was heated to 65° C. on a hot water bath, effecting completedissolution. The solution was slowly returned to room temperature andleft to stand overnight. The crystals that precipitated out werecollected by filtration and washed with a small amount of 2-propanol.The washed crystals were then placed in a desiccator and dried for 2hours under reduced pressure, giving 695 mg of white crystals.

The results of differential scanning analysis are shown in FIG. 5.

(iii) Fourth Preparation Method

About 30 mL of toluene was added to Compound 212 (700 mg) and themixture was heated to 65° C. on a hot water bath, effecting completedissolution. The solution was slowly returned to room temperature andleft to stand overnight. The crystals that precipitated out werecollected by filtration and washed with a small amount of toluene. Thewashed crystals were then placed in a desiccator and dried for 2 hoursunder reduced pressure, giving 440 mg of white crystals.

The results of powder x-ray diffraction analysis were as follows (FIG.6).

Diffraction angle (2θ): 8.6°, 14.2°, 17.5°, 18.3°, 19.7°, 22.3°, 30.9°,35.3°

The results of differential scanning analysis are shown in FIG. 7.

(iv) Fifth Preparation Method

About 2 mL of methanol and about 2 mL of water were added to Compound212 (50 mg) and the mixture was heated to 65° C. on a hot water bath,effecting dissolution. The solution was returned to room temperature andleft to stand overnight. The crystals that precipitated out werecollected by filtration, giving 16 mg of white crystals.

The results of differential scanning analysis are shown in FIG. 8.

Synthesis Example 14 Alternative Method for Step (1)

2-aminopyridine in an amount of 1.0 g (10.6 mmol) was dissolved in 10 mLof ethyl acetate, following which 1.78 mL (1.2 eq) of triethylamine wasadded, then 1.62 mL (1.1 eq) of trifluoroacetic anhydride was addedunder ice cooling. Stirring was subsequently carried out for 2 hours atroom temperature, then 10 mL of ethyl acetate and 10 mL of water wereadded, after which the mixture was again stirred and liquid-liquidextraction was carried out. The ethyl acetate phase was washed twicewith 10 mL of water, then dried over anhydrous magnesium sulfate andconcentrated under reduced pressure, giving 1.56 g of2,2,2-trifluoro-N-(pyridin-2(1H)-ylidene)acetamide (yield, 77.2%).

Synthesis Example 14 Alternative Method 2 for Step (1)

2-aminopyridine in an amount of 0.94 g (10 mmol) was dissolved in 20 mLof tetrahydrofuran (THF), following which 2.84 g (20 mmol) of ethyltrifluoroacetate and 1.22 g (10 mmol) of dimethylaminopyridine wereadded, and refluxing was carried out for 22 hours. THF was removed bydistillation, following which purification was carried out with a silicagel column (developing solvent: 4:1 solution of hexane and ethylacetate), giving 0.26 g of2,2,2-trifluoro-N-(pyridin-2(1H)-ylidene)acetamide (yield, 13.7%).

Synthesis Example 14 Alternative Method

2-chloro-5-chloromethylpyridine in an amount of 3.00 g (18.6 mmol) wasdissolved in 20 mL of anhydrous dimethylformamide (DMF), 1.75 g (18.6mmol) of 2-aminopyridine was added, and the mixture was stirred out at80° C. for 8 hours and at room temperature for 5 hours. Followingreaction completion, DMF was distilled off under reduced pressure andacetonitrile was added, whereupon a solid separated out. The solid wascollected by filtration, thoroughly washed with acetonitrile, thendried, giving 2.07 g of1-[(6-chloropyridin-3-yl)methyl]pyridin-2(1H)-imine hydrochloride(yield, 44%).

¹H-NMR (DMSO-d₆, δ, ppm): 5.65 (2H, s), 6.96 (1H, t), 7.23 (1H, m), 7.57(1H, d), 7.80 (1H, m), 7.91 (1H, m), 8.28 (1H, m), 8.49 (1H, d), 9.13(2H, brs)

An amount of 50 mg (0.20 mmol) of1-[(6-chloropyridin-3-yl)methyl]pyridin-2(1H)-imine hydrochlorideobtained by the above method was dissolved in 5 mL of anhydrousdichloromethane, 122 mg (1.00 mmol) of DMAP and 50 mg (0.24 mmol) oftrifluoroacetic anhydride were added in this order under ice cooling,and the mixture was stirred for 1 hour at room temperature. Followingreaction completion, the reaction mixture was diluted withdichloromethane, washed with 1% hydrochloric acid, then dried overanhydrous magnesium sulfate. Dichloromethane was removed by distillationunder reduced pressure, giving the target compound in an amount of 42 mg(yield, 67%). The NMR spectrum agreed with that of the product obtainedby the method described above.

Synthesis Example 152,2-dibromo-N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-acetamide(Compound 241)

An amount of 200 mg (0.78 mmol) of1-[(6-chloropyridin-3-yl)methyl]pyridin-2(1H)-imine hydrochlorideobtained in the method described under “Synthesis Example 14,Alternative Method,” 238 mg (1.95 mmol) of DMAP and 224 mg (1.17 mmol)of EDC-HCl were dissolved in 10 mL of anhydrous dichloromethane,following which 101 μL (202 mg, 1.17 mmol) of dibromoacetic acid wasadded and the mixture was stirred overnight at room temperature.Following reaction completion, the reaction mixture was diluted withdichloromethane, washed once with water and twice with 1% aqueous HCl,then dried over anhydrous magnesium sulfate and concentrated underreduced pressure, giving the target compound in an amount of 50 mg(yield, 15%).

¹H-NMR (CDCl₃, δ, ppm): 5.56 (2H, s), 5.99 (1H, s), 6.78 (1H, td), 7.33(1H, d), 7.69 (1H, td), 7.76 (1H, dd), 7.93 (1H, dd), 8.39 (1H, d), 8.50(1H, d)

¹³C-NMR (CDCl₃, δ, ppm): 44.6, 53.1, 113.7, 121.9, 124.8, 130.1, 138.2,139.7, 141.2, 149.5, 152.0, 159.4, 172.2

Synthesis Example 16N-[1-((6-chloro-5-fluoropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamide(Compound 227)

2-chloro-3-fluoro-5-methylpyridine in an amount of 4.00 g (27.6 mmol)was dissolved in 80 mL of carbon tetrachloride, following which 7.37 g(41.4 mmol) of N-bromosuccinimide and 20 mg of benzoyl peroxide wereadded and the mixture was refluxed overnight under heating. Followingreaction completion, the reaction mixture was returned to roomtemperature, concentrated under reduced pressure, and purified by silicagel column chromatography (hexane/ethyl acetate=19:1), giving 3.06 g of5-(bromomethyl)-2-chloro-3-fluoropyridine (yield, 51%).

¹H-NMR (CDCl₃, δ, ppm): 4.45 (2H, s), 7.54 (1H, dd), 8.23 (1H, s)

An amount of 50 mg (0.22 mmol) of5-(bromomethyl)-2-chloro-3-fluoropyridine obtained by the above methodwas dissolved in 5 mL of anhydrous acetonitrile, following which mg(0.22 mmol) of 2,2,2-trifluoro-N-(pyridin-2(1H)-ylidene)acetamideobtained by the method in “Synthesis Example 14, Step (1)” and 36 mg(0.26 mmol) of potassium carbonate were added in this order andrefluxing under heating was carried out for 7 hours. Following reactioncompletion, the reaction mixture was returned to room temperature, theinsoluble matter was filtered off, and the filtrate was concentratedunder reduced pressure. Diethyl ether was added to the resultingconcentrate, whereupon a solid separated out. The solid was collected byfiltration and washed with diethyl ether, then dried under reducedpressure in a desiccator, giving the target compound in an amount of 29mg (yield, 40%).

¹H-NMR (CDCl₃, δ, ppm): 5.54 (2H, s), 6.89 (1H, td), 7.76 (1H, dd), 7.80(1H, td), 7.85 (1H, d), 8.29 (1H, d), 8.57 (1H, d)

MS: m/z=334 (M+H)

Synthesis Example 17N-[1-((6-fluoropyridin-3-yl)methyl)pyridin-2(1H)-ylidene)-2,2,2-trifluoroacetamide(Compound 229)

2-fluoro-5-methylpyridine in an amount of 500 mg (4.50 mmol) wasdissolved in 50 mL of carbon tetrachloride, following which 1.20 g (6.76mmol) of N-bromosuccinimide and 20 mg of benzoyl peroxide were added andrefluxing under heating was carried out for 2.5 hours. Followingreaction completion, the reaction mixture was returned to roomtemperature, the solvent was removed by distillation under reducedpressure, and purification was carried out by silica gel columnchromatography (hexane/ethyl acetate=19:1), giving 300 mg of5-bromomethyl-2-fluoropyridine (yield, 35%).

An amount of 57 mg (0.30 mmol) of 5-bromomethyl-2-fluoropyridineobtained from the above method was dissolved in 10 mL of anhydrousacetonitrile, following which 57 mg (0.30 mmol) of2,2,2-trifluoro-N-(pyridin-2(1H)-ylidene)acetamide synthesized by themethod in “Synthesis Example 14, Step (1)” and 69 mg (0.50 mmol) ofpotassium carbonate were added in this order and the mixture wasrefluxed under heating for 6 hours. Following reaction completion, thereaction mixture was returned to room temperature, the insoluble matterwas filtered off, and the filtrate was concentrated under reducedpressure. Purification was carried out by silica gel columnchromatography (hexane/ethyl acetate=1:1→3:1), giving 21 mg of thetarget compound (yield, 23%).

¹H-NMR (CDCl₃, δ, ppm): 5.56 (2H, s), 6.89 (1H, td), 6.94 (1H, d), 7.79(1H, td), 7.87 (1H, d), 8.03 (1H, m), 8.31 (1H, s), 8.54 (1H, d)

MS: m/z=300 (M+H)

Synthesis Example 18N-[1-((6-bromopyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamide(Compound 231)

An amount of 500 mg (2.92 mmol) of 2-bromo-5-methylpyridine wasdissolved in 15 mL of carbon tetrachloride, following which 623 mg (3.50mmol) of N-bromosuccinimide and 10 mg of benzoyl peroxide were added andthe mixture was refluxed under heating for 19 hours. Following reactioncompletion, the reaction mixture was returned to room temperature andconcentrated under reduced pressure, then purified by silica gel columnchromatography (hexane/ethyl acetate=19:1), giving 143 mg of2-bromo-5-bromomethylpyridine (yield, 20%).

¹H-NMR (CDCl₃, δ, ppm): 4.42 (2H, s), 7.47 (1H, d), 7.59 (1H, dd), 8.38(1H, d)

An amount of 70 mg (0.28 mmol) of 2-bromo-5-bromomethylpyridine obtainedby the above method was dissolved in 10 mL of anhydrous acetonitrile,following which 54 mg (0.28 mmol) of2,2,2-trifluoro-N-(pyridin-2(1H)-ylidene)acetamide synthesized by themethod described in “Synthesis Example 14, Step (1)” and 46 mg (0.34mmol) of potassium carbonate were added in this order and refluxing wascarried out under heating for 6 hours. Following completion of thereaction, the reaction mixture was returned to room temperature, theinsoluble matter was removed by filtration, and the filtrate wasconcentrated under reduced pressure. Diethyl ether was then addedthereto, whereupon a solid separated out. The solid was collected byfiltration, washed with diethyl ether, then dried under reduced pressurein a desiccator, giving the target compound in an amount of 81 mg(yield, 82%).

¹H-NMR (CDCl₃, δ, ppm): 5.52 (2H, s), 6.88 (1H, t), 7.48 (1H, d), 7.78(2H, m), 7.84 (1H, d), 8.44 (1H, d), 8.53 (1H, d)

MS: m/z=360 (M+H)

Synthesis Example 192-chloro-N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]acetamide(Compound 236)

An amount of 70 mg (0.27 mmol) of1-[(6-chloropyridin-3-yl)methyl]pyridin-2(1H)-imine hydrochlorideobtained by the method described in “Synthesis Example 14, AlternativeMethod” was dissolved in 4 mL of anhydrous dichloromethane, followingwhich 82 mg (0.67 mmol) of DMAP, 25 mg (0.27 mmol) of chloroacetic acidand 62 mg (0.32 mmol) of EDC-HCl were added in this order, and themixture was stirred overnight at room temperature. Following reactioncompletion, the reaction mixture was diluted by adding dichloromethane,washed with water and 1% aqueous HCl, and dried over anhydrous magnesiumsulfate, then concentrated under reduced pressure, giving the targetcompound in an amount of 4 mg (yield, 5%).

¹H-NMR (CDCl₃, δ, ppm): 4.17 (2H, s), 5.46 (2H, s), 6.64 (1H, td), 7.31(1H, d), 7.60 (1H, td), 7.64 (1H, dd), 7.80 (1H, dd), 8.32 (1H, d), 8.45(1H, d)

MS: m/z=296 (M+H)

Synthesis Example 20N-[1-(1-(6-chloropyridin-3-yl)ethyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamide(Compound 237)

An amount of 44 mg (0.23 mmol) of2,2,2-trifluoro-N-(pyridin-2(1H)-ylidene)acetamide obtained by themethod in “Synthesis Example 14, Step (1)” was dissolved in 8 mL ofanhydrous acetonitrile, following which 72 mg (0.23 mmol) of1-(6-chloropyridin-3-yl)ethyl 4-methylbenzenesulfonate synthesized bythe method described in Biosci. Biotechnol. Biochem., 67(5), 980-988(2003) and 38 mg of potassium carbonate were added, and refluxing underheating was carried out for 100 minutes. Following reaction completion,the reaction mixture was returned to room temperature, the insolublematter was removed by filtration, and the filtrate was concentratedunder reduced pressure. The concentrate was purified by silica gelcolumn chromatography (hexane/ethyl acetate=3:1), giving the targetcompound in an amount of 24 mg (yield, 32%).

¹H-NMR (CDCl₃, δ, ppm): 1.89 (3H, d), 6.89 (1H, td), 7.08 (1H, q), 7.32(1H, d), 7.66 (1H, dd), 7.76 (2H, m), 8.44 (1H, d), 8.50 (1H, d)

¹³C-NMR (CDCl₃, δ, ppm): 19.2, 55.1, 115.1, 117.4 (q), 122.0, 124.8,133.7, 135.2, 138.4, 141.4, 148.6, 151.9, 159.1, 163.9 (q)

MS: m/z=330 (M+H)

Synthesis Example 21N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2-difluoroacetamide(Compound 238)

2-aminopyridine in an amount of 400 mg (4.26 mmol) was dissolved in 10mL of anhydrous dichloromethane, following which 322 μL (490 mg, 5.11mmol) of difluoroacetic acid, 982 mg (5.10 mmol) of EDC-HCl and 622 mg(5.11 mmol) of DMAP were added, and the mixture was stirred at roomtemperature for 61 hours. Following solution completion, the reactionmixture was diluted with dichloromethane, washed once with water andtwice with 1% aqueous HCl, then dried over anhydrous magnesium sulfate,and concentrated under reduced pressure, giving 102 mg of2,2-difluoro-N-(pyridin-2(1H)-ylidene)acetamide (yield, 14%).

¹H-NMR (CDCl₃, δ, ppm): 6.03 (1H, t), 7.15 (1H, m), 7.78 (1H, td), 8.20(1H, d), 8.34 (1H, dd), 8.72 (1H, brs)

An amount of 100 mg (0.58 mmol) of2,2-difluoro-N-(pyridin-2(1H)-ylidene)acetamide obtained by the abovemethod was dissolved in 10 mL of anhydrous acetonitrile, then 94 mg(0.58 mmol) of 2-chloro-5-chloromethylpyridine dissolved in 5 mL ofanhydrous acetonitrile was added, following which 84 mg (0.63 mmol) ofpotassium carbonate was added, and refluxing under heating was carriedout for 140 minutes. Following reaction completion, the reaction mixturewas returned to room temperature, the insoluble matter was removed byfiltration, and the filtrate was concentrated under reduced pressure.Ether was added to the concentrate, whereupon a solid separated out. Thesolid was collected by filtration and thoroughly dried, giving 63 mg ofthe target compound (yield, 37%).

¹H-NMR (CDCl₃, δ, ppm): 5.52 (2H, s), 5.90 (1H, t), 6.79 (1H, td), 7.33(1H, d), 7.71 (1H, m), 7.77 (1H, dd), 7.85 (1H, dd), 8.45 (1H, d), 8.50(1H, d)

¹³C-NMR (DMSO-d₆, δ, ppm): 53.0, 111.0 (t), 115.2, 120.7, 124.7, 131.7,140.6, 141.6, 143.2, 150.4, 150.9, 158.3, 169.4 (t)

MS: m/z=298 (M+H)

Synthesis Example 222-chloro-N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2-difluoroacetamide(Compound 239)

2-aminopyridine in an amount of 200 mg (2.13 mmol) was dissolved in 5 mLof dichloromethane, following which 491 mg (2.55 mmol) of EDC-HCl, 311mg (2.55 mmol) of DMAP and 187 μL (2.23 mmol, 290 mg) ofchlorodifluoroacetic acid were added in this order and the mixture wasstirred overnight. Following reaction completion, the reaction mixturewas diluted with dichloromethane, washed with water and 1% hydrochloricacid, then dried over anhydrous magnesium sulfate, giving 105 mg of2-chloro-2,2-difluoro-N-(pyridin-2(1H)-ylidene)acetamide (yield, 24%).

¹H-NMR (CDCl₃, δ, ppm): 7.19 (1H, dd), 7.82 (1H, m), 8.18 (1H, d), 8.36(1H, d), 9.35 (1H, brs)

An amount of 53 mg (0.33 mmol) of 2-chloro-5-chloromethylpyridinedissolved in 6 mL of anhydrous acetonitrile was added to 68 mg (0.33mmol) of 2-chloro-2,2-difluoro-N-(pyridin-2(1H)-ylidene)acetamidesynthesized by the above method, following which 50 mg (0.36 mmol) ofpotassium carbonate was added and refluxing under heating was carriedout for 1 hour. Following reaction completion, the reaction mixture wasreturned to room temperature then concentrated under reduced pressure.Diethyl ether was added to the concentrate, whereupon a solid separatedout. The solid was collected by filtration and dried, affording thetarget compound in an amount of 49 mg (yield, 45%).

¹H-NMR (CDCl₃, δ, ppm): 5.56 (2H, s), 6.92 (1H, t), 7.33 (1H, d), 7.82(1H, m), 7.91 (1H, dd), 8.02 (1H, d), 8.45 (1H, d), 8.48 (1H, d)

¹³C-NMR (CDCl₃, δ, ppm): 53.8, 115.2, 120.1 (t), 122.1, 124.8, 139.0,140.0, 142.3, 150.0, 151.9, 159.1, 159.1, 165.8 (t)

MS: m/z=332 (M+H)

Synthesis Example 232,2,2-trichloro-N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]acetamide(Compound 235)

An amount of 70 mg (0.27 mmol) of1-[(6-chloropyridin-3-yl)methyl]pyridin-2(1H)-imine hydrochlorideobtained by the method in “Synthesis Example 14, Alternative Method” wasdissolved in 4 mL of anhydrous dichloromethane, following which 94 μL(0.68 mmol, 68 mg) of triethylamine and 33 μg (0.27 mmol, 49 mg) oftrichloroacetyl chloride were added in this order, and the mixture wasstirred at room temperature for 1 hour. Following reaction completion,water was added, stopping the reaction, and liquid-liquid extraction wascarried out with dichloromethane and water. The organic phase was washedonce with water and twice with 1% hydrochloric acid, then dried overanhydrous magnesium sulfate and concentrated under reduced pressure.Diethyl ether was added to the concentrate, whereupon a solid separatedout. The solid was collected by filtration and dried, affording thetarget compound in an amount of 61 mg (yield, 62%).

¹H-NMR (CDCl₃, δ, ppm): 5.59 (2H, s), 6.86 (1H, t), 7.32 (1H, d), 7.78(1H, td), 7.91 (2H, m), 8.43 (1H, d), 8.50 (1H, d)

MS: m/z=364 (M+H)

Synthesis Example 24N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,3,3,3-pentafluoropropanamide(Compound 242)

2-aminopyridine (300 mg, 3.19 mmol) was dissolved in 15 mL of anhydrousdichloromethane, following which 919 mg (4.78 mmol) of EDC-HCl, 583 mg(4.78 mmol) of DMAP and 397 μL (628 mg, 3.83 mmol) ofpentafluoropropionic acid were added in this order and the mixture wasstirred overnight at room temperature. Following reaction completion,the reaction mixture was diluted with dichloromethane, washed once withwater and twice with 1% hydrochloric acid, then dried over anhydrousmagnesium sulfate and concentrated under reduced pressure, affording 85mg of 2,2,3,3,3-pentafluoro-N-(pyridin-2(1H)-ylidene)propanamide (yield,11%).

To 77 mg (0.32 mmol) of2,2,3,3,3-pentafluoro-N-(pyridin-2(1H)-ylidene)propanamide obtained bythe above method were added 52 mg (0.32 mmol) of2-chloro-5-chloromethylpyridine dissolved in 8 mL of anhydrousacetonitrile and 49 mg (0.35 mmol) of potassium carbonate, after whichthe mixture was refluxed under heating for 11 hours. Following reactioncompletion, the reaction mixture was returned to room temperature, theinsoluble matter was removed by filtration, and the filtrate wasconcentrated under reduced pressure. The concentrate was purified bysilica gel column chromatography (hexane/ethyl acetate 1:3), affordingthe target compound in an amount of 12 mg (yield, 10%).

¹H-NMR (CDCl₃, δ, ppm): 5.56 (2H, s), 6.90 (1H, td), 7.32 (1H, d), 7.79(2H, m), 7.84 (1H, d), 8.43 (1H, d), 8.56 (1H, d)

MS: m/z=366 (M+H)

Synthesis Example 25N-[1-((2-chloropyrimidin-5-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamide(Compound 243)

2-chloro-5-methylpyrimidine (1.04 g, 8.13 mmol) was dissolved in 30 mLof carbon tetrachloride, 1.73 g (9.75 mmol) of N-bromosuccinimide and 20mg of benzoyl peroxide were added, and the mixture was refluxed underheating for 6 hours. Following reaction completion, the reaction mixturewas returned to room temperature, concentrated under reduced pressure,and purified by silica gel column chromatography (hexane/ethylacetate=3:1), affording 641 mg of 5-bromomethyl-2-chloropyridine (yield,38%).

¹H-NMR (CDCl₃, δ, ppm): 4.42 (2H, s), 8.66 (2H, s)

An amount of 104 mg (0.50 mmol) of 5-bromomethyl-2-chloropyridineobtained by the above method was dissolved in 6 mL of anhydrousacetonitrile, after which 96 mg (0.50 mmol) of2,2,2-trifluoro-N-(pyridin-2(1H)-ylidene)acetamide obtained by themethod in “Synthesis Example 14, Step (1)” and 76 mg (0.55 mmol) ofpotassium carbonate were added, and the mixture was refluxed underheating for 1 hour. Following reaction completion, the reaction mixturewas returned to room temperature, the insoluble matter was removed byfiltration, and the filtrate was concentrated under reduced pressure.Diethyl ether was added to the concentrate, whereupon a solid separatedout. The solid was collected by filtration, washed with diethyl ether,then placed in a desiccator and dried under reduced pressure, affordingthe target compound in an amount of 92 mg (yield, 58%).

¹H-NMR (CDCl₃, δ, ppm): 5.54 (2H, s), 6.98 (1H, m), 7.87 (1H, m), 8.18(1H, m), 8.48 (1H, m), 8.83 (2H, m)

¹³C-NMR (CDCl₃, δ, ppm): 60.0, 115.6, 117.1 (q), 122.1, 127.5, 139.2,142.9, 158.8, 160.3 (2C), 161.4, 163.8 (q)

MS: m/z=317 (M+H)

Spectral data for compounds obtained by methods similar to those inSynthesis Examples 14 to 25 are shown in Tables 10 and 11.

TABLE 10 No. ¹NMR (CDCl₃, δ, ppm) IR(KBr, v, cm⁻¹) or MS 212 5.57 (2H,s), 6.92 (1H, td), 7.31 (1H, d), 7.80 (1H, td), m/z = 316 (M + H) 7.87(1H, dd), 7.99 (1H, dd), 8.48 (2H, m) 213 5.61 (2H, s), 6.93 (1H, dd),7.68 (1H, s), 7.83 (1H, td), m/z = 322 (M + H) 7.97 (1H, d), 8.53 (1H,d) 214 3.74 (3H, s), 5.40 (2H, s), 6.45 (1H, td), 7.29 (1H, d), m/z =278 (M + H) 7.46 (2H, m), 7.73 (1H, dd), 8.12 (1H, dd), 8.40 (1H, d) 2155.53 (2H, s), 7.34 (1H, d), 7.71 (1H, dd), 7.87 (1H, dd), m/z = 350 (M +H) 7.94 (1H, s), 8.49 (1H, d), 8.55 (1H, s) 216 5.54 (2H, s), 7.34 (1H,d), 7.70 (1H, m), 7.80 (1H, m), m/z = 334 (M + H) 7.88 (1H, dd), 8.48(1H, d), 8.64 (1H, m) 217 5.49 (2H, s), 6.85 (1H, dd), 7.35 (1H, d),7.76 (1H, dd), m/z = 350 (M + H) 7.85 (1H, dd), 8.44 (1H, d), 8.62 (1H,s) 218 5.56 (2H, s), 7.68 (1H, s), 7.74 (1H, dd), 7.84 (1H, d), m/z =356 (M + H) 8.58 (1H, d) 219 5.60 (2H, s), 7.69 (1H, s), 7.72 (1H, td),7.86 (1H, m), m/z = 340 (M + H) 8.67 (1H, m) 220 5.58 (2H, s), 6.90 (1H,d), 7.67 (1H, s), 7.90 (1H, d), m/z = 356 (M + H) 8.61 (1H, s) 221 2.31(3H, s), 5.50 (2H, s), 6.98 (1H, m), 7.34 (1H, d), m/z = 330 (M + H)7.73 (1H, dd), 7.77 (2H, m), 8.42 (1H, d) 222 2.40 (3H, S), 5.49 (2H,s), 6.70 (1H, dd), 7.32 (1H, d), m/z = 330 (M + H) 7.70 (1H, d), 7.86(1H, dd), 8.37 (1H, s), 8.43 (1H, d) 223 2.29 (3H, s), 5.52 (2H, s),7.32 (1H, d), 7.62 (1H, s), m/z = 330 (M + H) 7.65 (1H, dd), 7.88 (1H,dd), 8.46 (1H, d), 8.50 (1H, d) 224 5.58 (2H, s), 6.81 (1H, m), 7.37(4H, m), 7.77 (2H, m), m/z = 281 (M + H) 8.50 (1H, d) 225 5.52 (2H, s),6.85 (1H, m), 7.30 (2H, d), 7.36 (2H, d), m/z = 315 (M + H) 7.75 (1H,td), 7.84 (1H, d), 8.47 (1H, d) 226 5.57 (2H, s), 6.86 (1H, m),7.26-7.35 (2H, m), 7.78 (1H, td), m/z = 282 (M + H) 7.86 (1H, m), 8.63(2H, m), 8.67 (1H, d) 227 5.54 (2H, s), 6.89 (1H, td), 7.76 (1H, dd),7.80 (1H, td), m/z = 334 (M + H) 7.85 (1H, d), 8.29 (1H, d), 8.57 (1H,d) 228 5.62 (2H, s), 6.90 (1H, t), 7.69 (1H, d), 7.81 (1H, t), m/z = 350(M + H) 7.88 (1H, d), 8.06 (1H, d), 8.56 (1H, d), 8.78 (1H, s) 229 5.56(2H, s), 6.89 (1H, td), 6.94 (1H, d), 7.79 (1H, td), m/z = 300 (M + H)7.87 (1H, d), 8.03 (1H, m), 8.31 (1H, s), 8.54 (1H, d) 230 5.49 (2H, s),6.89 (1H, t), 7.79-7.90 (2H, m), 8.04 (1H, d), m/z = 350 (M + H) 8.37(1H, d), 8.56 (1H, m) 231 5.52 (2H, s), 6.88 (1H, t), 7.48 (1H, d), 7.78(2H, m), m/z = 360 (M + H) 7.84 (1H, d), 8.44 (1H, d), 8.53 (1H, d) 2325.52 (2H, s), 6.71 (1H, m), 7.35 (1H, d), 7.86 (1H, dd), m/z = 334 (M +H) 7.94 (1H, m), 8.33 (1H, dd), 8.44 (1H, d) 233 5.53 (2H, s), 6.74 (1H,m), 7.33 (1H, d), 7.87 (1H, dd), m/z = 334 (M + H) 8.07 (1H, m), 8.29(1H, dd), 8.45 (1H, d) 234 5.54 (2H, s), 6.02 (1H, s), 6.77 (1H, t),7.32 (1H, m), m/z = 330 (M + H) 7.69 (1H, m), 7.77 (1H, d), 7.89 (1H,m), 8.42 (1H, m), 8.49 (1H, s)

TABLE 11 No. ¹NMR (CDCl₃, δ, ppm) IR(KBr, v, cm⁻¹) or MS 235 5.59 (2H,s), 6.86 (1H, t), 7.32 (1H, d), 7.78 (1H, td), 7.91 (2H, m), m/z = 364(M + H) 8.43 (1H, d), 8.50 (1H, d) 236 4.17 (2H, s), 5.46 (2H, s), 6.64(1H, td), 7.31 (1H, d), 7.60 (1H, m/z = 296 (M + H) td), 7.64 (1H, dd),7.80 (1H, dd), 8.32 (1H, d), 8.45 (1H, d) 237 1.89 (3H, d), 6.89 (1H,td), 7.08 (1H, q), 7.32 (1H, d), 7.66 (1H, m/z = 330 (M + H) dd), 7.76(2H, m), 8.44 (1H, d), 8.50 (1H, d) 238 5.52 (2H, s), 5.90 (1H, t), 6.79(1H, td), 7.33 (1H, d), 7.71 (1H, m), m/z = 298 (M + H) 7.77 (1H, dd),7.85 (1H, dd), 8.45 (1H, d), 8.50 (1H, d) 239 5.56 (2H, s), 6.92 (1H,t), 7.33 (1H, d), 7.82 (1H, m), 7.91 (1H, dd), m/z = 332 (M + H) 8.02(1H, d), 8.45 (1H, d), 8.48 (1H, d) 240 5.53 (1H, d), 5.58 (1H, d), 6.06(1H, s), 6.76 (1H, td), 7.32 (1H, d), m/z = 374 (M + H) 7.69 (1H, m),7.70 (1H, m), 7.90 (1H, dd), 8.40 (1H, d), 8.50 (1H, d) 241 5.56 (2H,s), 5.99 (1H, s), 6.78 (1H, td), 7.33 (1H, d), 7.69 (1H, m/z = 418 (M +H) td), 7.76 (1H, dd), 7.93 (1H, dd), 8.39 (1H, d), 8.50 (1H, d) 2425.56 (2H, s), 6.90 (1H, td), 7.32 (1H, d), 7.79 (2H, m), 7.84 (1H, d),m/z = 366 (M + H) 8.43 (1H, d), 8.56 (1H, d) 243 5.54 (2H, s), 6.98 (1H,m), 7.87 (1H, m), 8.18 (1H, m), 8.48 (1H, m), m/z = 317 (M + H) 8.83(2H, m) 244 4.17 (2H, s), 5.46 (2H, s), 6.63 (1H, td), 7.31 (1H, d),7.60 (1H, td), 7.65 (1H, dd), 7.80 (1H, dd), 8.32 (1H, d), 8.47 (1H, d)

Comparative Example 1 N-[(6-chloropyridin-3-yl)methyl]cyanamide (JP2003-26661 A, Compound 1)

Cyanogen bromide (220 mg, 2.09 mmol) was dissolved in 10 mL of anhydrouschloroform, and the solution was cooled to 0° C. To this was dropwiseadded a solution of 500 mg (3.49 mmol) of 2-chloro-5-aminomethylpyridinedissolved in 10 mL of anhydrous chloroform, and the resulting mixturewas stirred at 0° C. for 1 hour. The reaction mixture was filtered, thenwater was added and liquid-liquid extraction was carried out, followingwhich the chloroform phase was dried over anhydrous magnesium sulfateand concentrated under reduced pressure. The concentrate was purified bysilica gel column chromatography (hexane/ethyl acetate=1:1), giving 122mg (yield, 35%) of the target compound.

¹H-NMR (CDCl₃, δ, ppm): 4.21 (2H, s), 5.74 (1H, brs), 7.36 (1H, d), 7.71(1H, dd), 8.30 (1H, d)

¹³C-NMR (CDCl₃, δ, ppm): 46.5, 116.1, 124.8, 131.5, 138.9, 148.9, 151.4

MS: m/z=166 (M−H)

Comparative Example 2N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]cyanamide(Patent Document 6, Compound 20)

An amount of 128 mg (0.58 mmol) of1-[(6-chloropyridin-3-yl)methyl]pyridine-2(1H)-imine obtained by thealternative method described in Synthesis Example 14 was dissolved in 5mL of anhydrous dimethylformamide, NaH (as a 60% dispersion in oil) wasadded in an amount of 40 mg (net weight, 24 mg; 1.04 mmol), and themixture was stirred at room temperature for 30 minutes. Next, 60 mg(0.57 mmol) of cyanogen bromide was added, and the resulting mixture wasstirred overnight. Following reaction completion, water and ethylacetate were added to the reaction mixture and liquid-liquid extractionwas carried out. The organic phase was dried over anhydrous magnesiumsulfate, then concentrated under reduced pressure. The concentrate waspurified on a TLC plate (one 0.5 mm plate, developed with 100% ethylacetate), giving 14 mg of the target compound (yield, 10%).

¹H-NMR (CDCl₃, δ, ppm): 5.28 (2H, s), 6.55 (1H, m), 7.33 (2H, m), 7.56(2H, m), 7.75 (1H, dd), 8.40 (1H, d)

Comparative Example 3N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(2H)-ylidene]acetamide(Patent Document 4, Compound 2)

Anhydrous dichloromethane (20 mL) was added to 118 mg (0.46 mmol) of1-[(6-chloropyridin-3-yl)methyl]pyridine-2(1H)-imine hydrochlorideobtained by the alternative method described in Synthesis Example 14,following which 159 μL (1.16 mmol, 116 mg) of triethylamine and 33 μL ofacetyl chloride were added and the mixture was stirred at roomtemperature for 15 minutes. The reaction was stopped by adding water tothe reaction mixture, and liquid-liquid extraction was carried out withchloroform and water. The organic phase was washed with a saturatedaqueous solution of ammonium chloride, then concentrated. With theaddition of hexane thereto, a solid settled out. The solid was collectedby filtration and washed, then thoroughly dried, giving 21 mg of thetarget compound (yield, 17%).

¹H-NMR (CDCl₃, δ, ppm): 2.21 (3H, s), 5.35 (2H, s), 6.46 (1H, m), 7.32(1H, d), 7.48 (2H, m), 7.75 (1H, d), 8.10 (1H, dd), 8.45 (1H, dd)

MS: m/z=262 (M+H)

Comparative Example 43-[1-((6-chloropyridin-3-yl)methyl)imidazolidin-2-ylidene]-1,1,1-trifluoropropan-2-one(Patent Document 5, Example 4)

Anhydrous dimethylformamide (15 mL) was added to 1.30 g (33.9 mmol, 780mg) of NaH (as a 60% dispersion in oil), and the mixture was cooled to0° C. To this was dropwise added 1.52 mL (1.90 g, 17.0 mmol) of1,1,1-trifluoroacetone, and stirring was carried out at 0° C. for 10minutes. To this was added 7.0 mL (110 mmol, 8.35 g) of carbondisulfide, and stirring was carried out at 50° C. for 1 hour. Next, thereaction mixture was cooled to 0° C., 2.1 mL (34.0 mmol, 4.81 g) ofmethyl iodide was added, and the mixture was stirred overnight at roomtemperature. Following reaction completion, the reaction mixture waspoured into ice water and stirring was carried out until the icecompletely melted. The reaction mixture was transferred to a separatoryfunnel and extracted with ethyl acetate. The organic phase was washedwith saturated saline, then dried over anhydrous magnesium sulfate andconcentrated under reduced pressure. The concentrate was purified bysilica gel chromatography (hexane/ethyl acetate=95:5), and the fractionscontaining the target compound were collected and concentrated underreduced pressure. Hexane was added thereto, whereupon a solid settledout. The solid was collected by filtration and washed with hexane, thenthoroughly dried, giving 460 mg (yield, 13%) of1,1,1-trifluoro-4,4-bis(methylthio)-3-buten-2-one.

¹H-NMR (CDCl₃, δ, ppm): 2.56 (3H, s), 2.58 (2H, s), 6.25 (1H, s)

Next, 20 mL of ethylenediamine was added to 2.0 g (12.4 mmol) of2-chloro-5-chloromethylpyridine, and the mixture was stirred overnight.Following reaction completion, the reaction mixture was concentratedunder reduced pressure, after which acetonitrile was added and insolublematter were removed by filtration. The filtrate was concentrated underreduced pressure, giving 2.45 g (yield, 100%) ofN-((6-chloropyridin-3-yl)methyl)ethane-1,2-diamine.

A solution of 77 mg (0.42 mmol) of theN-((6-chloropyridin-3-yl)methyl)ethane-1,2-diamine obtained by theforegoing method in 8 mL of anhydrous acetonitrile was added to 60 mg(0.28 mmol) of 1,1,1-trifluoro-4,4-bis(methylthio)-3-buten-2-oneobtained by the foregoing method, and the mixture was refluxed underheating for 40 minutes. Following reaction completion, the reactionmixture was returned to room temperature and concentrated under reducedpressure, after which ethyl acetate and water were added, andliquid-liquid extraction was carried out. The organic phase was washedwith anhydrous magnesium sulfate, then concentrated under reducedpressure, and the concentrate was purified by silica gel columnchromatography (hexane/ethyl acetate=3:1), giving 59 mg of the targetcompound (yield, 69%).

¹H-NMR (CDCl₃, δ, ppm): 3.49 (2H, t), 3.78 (2H, t), 4.40 (2H, s), 5.13(1H, s), 7.37 (1H, d), 7.56 (1H, dd), 8.31 (1H, d), 9.34 (1H, brs)

m/z=306 (M+H)

Comparative Example 53-[3-((6-chloropyridin-3-yl)methyl)thiazolidin-2-ylidene]-1,1,1-trifluoropropan-2-one(Patent Document 5, Example 3)

A solution of 36 mg (0.46 mmol) of 2-aminoethanethiol dissolved in 10 mLof ethanol was added to 100 mg (0.46 mmol) of1,1,1-trifluoro-4,4-bis(methylthio)-3-buten-2-one obtained by the methoddescribed in Comparative Example 4, and the mixture was refluxed underheating for 6 hours, then stirred at room temperature for 13 hours.Following reaction completion, the ethanol was distilled off underreduced pressure, after which the condensate was dissolved in ethylacetate and washed once with water. The washed product was dried overanhydrous magnesium sulfate, then concentrated under reduced pressure,giving 73 mg (yield, 81%) of1,1,1-trifluoro-3-(thiazolidin-2-ylidene)propan-2-one.

¹N-NMR (CDCl₃, δ, ppm): 3.35 (2H, m), 4.02 (2H, m), 5.61 (1H, s), 10.40(1H, brs),

2-chloro-5-chloromethylpyridine (80 mg, 0.50 mmol) dissolved in 8 mL ofanhydrous acetonitrile, and potassium carbonate (69 mg, 0.50 mmol) wereadded to 65 mg (0.33 mmol) of1,1,1-trifluoro-3-(thiaolidin-2-ylidene)propane-2-one obtained by theforegoing method, and the mixture was refluxed under heating for 2hours. After reaction completion, the reaction mixture was returned toroom temperature, insoluble matter was removed by filtration, and thefiltrate was concentrated under reduced pressure. The concentrate waspurified by silica gel column chromatography (hexane/ethylacetate=1:1→1:3), giving 53 mg of the target compound (yield, 50%).

¹H-NMR (CDCl₃, δ, ppm): 3.20 (2H, t), 3.73 (2H, t), 4.61 (2H, s), 5.80(1H, s), 7.36 (1H, d), 7.53 (1H, dd), 8.31 (1H, d)

MS: m/z=323 (M+H)

Comparative Example 63-[1-((6-chloropyridin-3-yl)methyl)imidazolidin-2-ylidene]-1,1,1,5,5,5-hexafluoropentan-2,4-dione(Patent Document 5, Example 5)

An amount of 31 mg (0.10 mmol) of the3-[1-((6-chloropyridin-3-yl)methyl)imidazolidin-2-ylidene]-1,1,1-trifluoropropan-2-oneobtained by the method described in Comparative Example 4 was dissolvedin 2 mL of anhydrous dichloromethane, then 20 μL (0.25 mmol, 20 mg) ofpyridine and 28 μL (0.20 mmol, 42 mg) of trifluoroacetic anhydride wereadded in this order, and the mixture was stirred at room temperature for30 minutes. The progress of the reaction was checked by thin layerchromatography, whereupon there was found to be some starting materialremaining in the system. As a result, another 84 μL (0.60 mmol, 62 mg)of trifluoroacetic anhydride was added, and stirring was carried out for1 hour at room temperature. Following reaction completion, the reactionmixture was concentrated under reduced pressure, then purified on a TLCplate (one 0.5 mm plate, developed with hexane/ethyl=2:8), giving 30 mgof the target compound (yield, 75%).

¹H-NMR (CD₃OD, δ, ppm): 3.87 (4H, m), 4.51 (2H, s), 7.50 (1H, d), 7.82(1H, dd), 8.35 (1H, d)

MS: m/z=402 (M+H)

Comparative Example 7N-[1-((6-chloropyridin-3-yl)methyl)imidazolidin-2-ylidene]-2,2,2-trifluoroacetamide(Patent Document 5, Example 7)

Dimethylcarbonimidodithioate methanesulfonic acid chloride (4.25 g, 18.2mmol) was dissolved in 30 mL of pyridine, 3.80 mL (5.73 g, 27.3 mmol) oftrifluoroacetic anhydride was added dropwise, and the mixture wasstirred overnight at room temperature. The reaction mixture wasconcentrated under reduced pressure, and subjected to liquid-liquidextraction using dichloromethane and water. The resulting organic phasewas dried over anhydrous magnesium sulfate, then concentrated, giving5.36 g of dimethyl(2,2,2-trifluoroacetyl)carbonimidodithioate (yield,100%).

N-((6-chloropyridin-3-yl)methyl)ethane-1,2-diamine (4.61 g, 24.9 mmol)was synthesized by the method described in Comparative Example 4. Thiswas dissolved in 40 mL of anhydrous acetonitrile, 4.60 g (21.3 mmol) ofthe dimethyl(2,2,2-trichloroacetyl)carbonimidodithioate obtained by theabove method was added, and the resulting mixture was refluxed underheating for 90 minutes. Following reaction completion, the reactionmixture was returned to room temperature, after which the solvent wasdistilled off under reduced pressure. The solid that settled out wascollected by filtration and washed with a small amount of acetonitrile,giving 2.17 g of the target compound (yield, 33%).

¹H-NMR (CDCl₃, δ, ppm): 3.50 (2H, m), 3.76 (2H, m), 4.60 (2H, s), 7.34(1H, d), 7.70 (1H, dd), 8.33 (1H, d)

Melting point: 168 to 170° C.

Comparative Example 8N-[3-((6-chloropyridin-3-yl)methyl)thiazolidin-2-ylidene]-2,2,2-trifluoroacetamide(Patent Document 5, Example 6)

Ethanol (20 mL) was added to 77 mg (1.0 mmol) of 2-aminoethanethiol, 216mmol (1.0 mmol) of thedimethyl(2,2,2-trifluoroacetyl)carbonimidodithioate synthesized by themethod described in Comparative Example 7 was added, and the mixture wasstirred overnight at room temperature. Following reaction completion,the solvent was distilled off under reduced pressure, and purificationwas carried out by silica gel column chromatography (hexane/ethylacetate=1:1), giving 100 mg of2,2,2-trifluoro-N-(thiazolidin-2-ylidene)acetamide (yield, 51%). Thisreaction was carried out once more by the same synthesis method, givinga combined amount of 350 mg of2,2,2-trifluoro-N-(thiazolidin-2-ylidene)acetamide.

Dimethylformamide (2 mL) and tetrahydrofuran (18 mL) were added to 162mg (0.82 mmol) of 2,2,2-trifluoro-N-(thiazolidin-2-ylidene)acetamideobtained by the above-described method, following which 198 mg of2-chloro-5-chloromethylpyridine and 150 mg (1.09 mmol) of potassiumcarbonate were added, and the mixture was refluxed under heating for 20hours. Following reaction completion, the reaction mixture was returnedto room temperature, insoluble matter was filtered off, and the filtratewas concentrated under reduced pressure. The concentrate was purified ona TLC plate (two 0.5 mm plates, developed with 100% ethyl acetate),giving 230 mg of the target compound (yield, 87%).

¹H-NMR (CDCl₃, δ, ppm): 3.27 (2H, m), 3.73 (2H, m), 4.86 (2H, s), 7.36(1H, d), 7.72 (1H, dd), 8.36 (1H, d)

Melting point: 96° C.

EXAMPLE FORMULATIONS Formulation Example 1 Granules

Compound 1  5 wt % Bentonite 40 wt % Talc 10 wt % Clay 43 wt % Calciumligninsulfonate  2 wt %

The above ingredients were uniformly ground and mixed, following whichwater was added and the mixture was thoroughly kneaded. The kneadedmaterial was granulated and dried, giving granules.

Formulation Example 2 Granules

Compound 212   2 wt % Sanx P-252   5 wt % Binder 1.5 wt % Granulationenhancer 0.5 wt % Clay  91 wt %

The above ingredients were uniformly ground and mixed, following whichwater was added and the mixture was thoroughly kneaded. The kneadedmaterial was granulated and dried, giving granules.

Formulation Example 3 Wettable Powder

Compound 3 30 wt % Clay 50 wt % White carbon  2 wt % Diatomaceous earth13 wt % Calcium ligninsulfonate  4 wt % Sodium lauryl sulfate  1 wt %

The above ingredients were uniformly mixed and ground, giving a wettablepowder.

Formulation Example 4 Water Dispersible Granules

Compound 212 30 wt %  Clay 60 wt %  Dextrin 5 wt % Alkyl-maleic acidcopolymer 4 wt % Sodium lauryl sulfate 1 wt %

The above ingredients were uniformly ground and mixed, following whichwater was added and the mixture was thoroughly kneaded. The kneadedmaterial was granulated and dried, giving water dispersible granules.

Formulation Example 5 Flowable Concentrate

Compound 8 25 wt %  POE polystyryl phenyl ether sulfate 5 wt % Propyleneglycol 6 wt % Bentonite 1 wt % Xanthan gum, 1% aqueous solution 3 wt %PRONAL EX-300 (Toho Chemical Industry Co., 0.05 wt %   Ltd.) ADDAC 827(KI Chemical Industry Co., Ltd.) 0.02 wt %   Water added to 100 wt %

The entire amounts of the above ingredients, excluding the 1% aqueoussolution of xanthan gum and a suitable amount of water, were premixed,then ground in a wet grinding mill. The 1% aqueous solution of xanthangum and the remaining water were then added to the total amount of 100wt %, giving a flowable concentration.

Formulation Example 6 Emulsifiable Concentrate

Compound 1 15 wt % N,N-dimethylformamide 20 wt % Solvesso 150 (ExxonMobil Yugen Kaisha) 55 wt % Polyoxyethylene alkyl aryl ether 10 wt %

The above ingredients were uniformly mixed and dissolved, giving anemulsifiable concentrate.

Formulation Example 7 Dust Formulation

Compound 14  2 wt % Clay 60 wt % Talc 37 wt % Calcium stearate  1 wt %

The above ingredients were uniformly mixed, giving a dust formulation.

Formulation Example 8 Low-Drift Dust Formulation

Compound 1 2 wt % Low-drift clay 94.5 wt %   White carbon 2 wt % Calciumstearate 1 wt % Light liquid paraffin 0.5 wt %  

The above ingredients were uniformly mixed, giving a dust formulation.

Formulation Example 9 Fine Granules F

Compound 3 2 wt % Carrier 94 wt %  White carbon 2 wt % Hisol SAS-296 2wt %

The above ingredients were uniformly mixed, giving a dust formulation.

Formulation Example 10 Liquid Formulation for Drop

Compound 1 10 wt % Benzyl alcohol 74.9 wt %   Propylene carbonate 15 wt% BHT 0.1 wt % 

The above ingredients were uniformly mixed, giving a liquefied dropformulation.

Formulation Example 11 Liquid Formulation for Drop

Compound 212 48 wt % Ethanol 52 wt %

The above ingredients were uniformly mixed, giving a liquefied dropformulation.

In addition, an example of a mixed formulation containing both acompound of the present invention and another pest control agent isprovided below.

Formulation Example 12 Granules

Compound 212   2 wt % Propenazole  24 wt % Binder 3.0 wt % Granulationenhancer 0.5 wt % Clay 70.5 wt % 

The above ingredients were uniformly ground and mixed, following whichwater was added and the mixture was thoroughly kneaded. The kneadedmaterial was granulated and dried, giving granules.

TEST EXAMPLES Foliar Application Tests Test Example 1-1 Diamondback MothControl Test

Leaf discs 5.0 cm in diameter were cut from cabbage plants grown inpots, and these were sprayed with solutions of the inventive compoundsat a predetermined concentration prepared to 50% acetone/water(containing 0.05% Tween 20). The treated leaf discs were air dried,following which second-instar larvae were released onto the discs. Theleaf discs and larvae were then held in an incubation chamber at 25° C.(16-hour period of light, 8-hour dark period). Three days afterreleased, the numbers of live and dead insects were counted, and themortality was calculated from the following formula. This was atwo-replication test.Mortality(%)=[number of dead insects/(number of live insects+number ofdead insects)]×100

From these results, with 500 ppm foliar application, Compounds 9, 10,49, 196, 211, 81, 82, 89, 92, 104, 107, 108, 109, 110, 111, 112, 114,128, 131, 140, 141, 144, 145, 146, 152, 165, 167, 170, 171, 172, 176,179, 180, 181, 183, 184, 186, 188, 189, 190, 193, 194, 212, 219, 226,227, 229, 230, 234, 235, 237, 239, 240, 241, 242 and 243 exhibitedinsecticidal activities having at least 80% mortality.

Test Example 1-2 Diamondback Moth Control Test

Leaf discs 5.0 cm in diameter were cut from cabbage plants grown inpots, and these were sprayed with solutions of the inventive compoundsat a predetermined concentration prepared to 50% acetone/water(containing 0.05% Tween 20). The treated leaf discs were air dried,following which second-instar larvae were released onto the discs. Theleaf discs and larvae were then held in an incubation chamber at 25° C.(16-hour period of light, 8-hour dark period). Three days afterreleased, the numbers of live and dead insects were counted, and themortality was calculated from the following formula. This was atwo-replication test.Mortality(%)=[number of dead insects/(number of live insects+number ofdead insects)]×100

From these results, with 100 ppm foliar application, Compounds 81, 89,92, 107, 111, 112, 114, 128, 152, 171, 183, 184, 186, 189, 190, 193,194, 211, 212, 213, 215, 216, 218, 219, 227, 229, 230, 231, 234, 235,237, 238, 239, 242 and 243 exhibited insecticidal activities having atleast 80% mortality.

Test Example 2 Common Cutworm Control Test

Leaf discs 5.0 cm in diameter were cut from cabbage plants grown inpots, and these were sprayed with solutions of the inventive compoundsat a predetermined concentration prepared to 50% acetone/water(containing 0.05% Tween 20). The treated leaf discs were air dried,following which third-instar larvae were released onto the discs. Theleaf discs and larvae were then held in an incubation chamber at 25° C.(16-hour period of light, 8-hour dark period). Three days afterreleased, the numbers of live and dead insects were counted, and themortality was calculated from the following formula. This was atwo-replication test.Mortality(%)=[number of dead insects/(number of live insects+number ofdead insects)]×100

From these results, with 500 ppm foliar application, Compounds 46, 202,68, 82, 89, 92, 96, 104, 108, 128, 140, 176, 184, 189, 190, 193, 212,219, 227, 229, 230 and 239 exhibited insecticidal activities having atleast 80% mortality.

Test Example 3-1 Cotton Aphid Control Test

Leaf discs 2.0 cm in diameter were cut from cucumber plants grown inpots, and these were sprayed with solutions of the inventive compoundsat a predetermined concentration prepared to 50% acetone/water(containing 0.05% Tween 20). The treated leaf discs were air dried,following which first-instar larvae were released onto the discs. Theleaf discs and larvae were then held in an incubation chamber at 25° C.(16-hour period of light, 8-hour dark period). Three days afterreleased, the numbers of live and dead insects were counted, and themortality was calculated from the following formula. This was atwo-replication test.Mortality(%)=[number of dead insects/(number of live insects+number ofdead insects)]×100

From these results, with 500 ppm foliar application, Compounds 1, 2, 3,6, 7, 8, 9, 10, 12, 14, 15, 18, 20, 21, 22, 25, 27, 29, 30, 31, 32, 33,34, 36, 37, 41, 42, 43, 44, 45, 46, 49, 50, 52, 58, 61, 68, 69, 71, 72,73, 76, 77, 79, 81, 82, 83, 85, 88, 89, 92, 96, 100, 101, 102, 103, 104,119, 122, 131, 132, 135, 139, 165, 167, 170, 179, 182, 183, 184, 186,189, 192, 193, 194, 196, 199, 200, 202, 208, 210, 211, 212, 219, 221,222, 223, 225, 226, 227, 228, 229, 230, 233, 234, 235, 237, 239 and 243exhibited insecticidal activities having at least 80% mortality.

By contrast, when Compound 1 (N-[(6-chloropyridin-3-yl)methyl]cyanamide)in Patent Document 1 (Japanese Patent Application Publication No.2003-26661) was tested by the same method, the cotton aphid mortalityfrom foliar application at 500 ppm was 65%.

Test Example 3-2 Cotton Aphid Control Test

Leaf discs 2.0 cm in diameter were cut from cucumber plants grown inpots, and these were sprayed with solutions of the inventive compoundsat a predetermined concentration prepared to 50% acetone/water(containing 0.05% Tween 20). The treated leaf discs were air dried,following which first-instar larvae were released onto the discs. Theleaf discs and larvae were then held in an incubation chamber at 25° C.(16-hour period of light, 8-hour dark period). Three days afterreleased, the numbers of live and dead insects were counted, and themortality was calculated from the following formula. This was atwo-replication test.Mortality(%)=[number of dead insects/(number of live insects+number ofdead insects)]×100

From these results, with 100 ppm foliar application, Compounds 1, 2, 3,6, 7, 8, 9, 10, 14, 245, 18, 21, 34, 43, 49, 50, 71, 76, 83, 85, 86, 88,89, 90, 91, 92, 93, 94, 96, 97, 102, 105, 113, 128, 131, 137, 138, 139,140, 141, 145, 149, 152, 157, 163, 183, 186, 196, 199, 200, 204, 208,212, 213, 214, 215, 216, 219, 222, 223, 225, 226, 227, 228, 229, 230,232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243 and 244exhibited insecticidal activities having at least 80% mortality.

Test Example 3-3 Cotton Aphid Control Test

Leaf discs 2.0 cm in diameter were cut from cucumber plants grown inpots, and these were sprayed with solutions of the inventive compoundsat a predetermined concentration prepared to 50% acetone/water(containing 0.05% Tween 20). The treated leaf discs were air dried,following which first-instar larvae were released onto the discs. Theleaf discs and larvae were then held in an incubation chamber at 25° C.(16-hour period of light, 8-hour dark period). Three days afterreleased, the numbers of live and dead insects were counted, and themortality was calculated from the following formula. This was atwo-replication test.Mortality(%)=[number of dead insects/(number of live insects+number ofdead insects)]×100

From these results, with 20 ppm foliar application, Compounds 1, 2, 3,6, 7, 8, 14, 18, 21, 82, 86, 88, 89, 90, 91, 94, 95, 128, 137, 138, 157,199, 200, 212, 213, 214, 219, 226, 227, 229, 230, 231, 233, 234, 235,236, 237, 238, 239, 240, 241, 242, 243 and 244 exhibited insecticidalactivities having at least 80% mortality.

Test Example 4 Green Peach Aphid Control Test

Leaf discs 2.8 cm in diameter were cut from cabbage plants grown inpots, and four adult aphids were released onto each disc. One day later,the adults were removed, and the number of first-instar larvae that hadbeen deposited on each leaf disc was adjusted to 10. Next, the leafdiscs parasitized by these first instar larvae were sprayed withsolutions of the inventive compounds at a predetermined concentrationprepared to 50% acetone/water (containing 0.05% Tween 20). The treatedleaf discs were air dried, following which covers were placed over thePetri dishes and the leaf discs and larvae were held in an incubationchamber at 25° C. (16-hour period of light, 8-hour dark period). Threedays after released, the numbers of live and dead insects were counted,and the mortality was calculated from the following formula. This was atwo-replication test.Mortality(%)=[number of dead insects/(number of live insects+number ofdead insects)]×100

From these results, with 100 ppm foliar application, Compounds 1, 2, 3,6, 7, 8, 9, 10, 11 and 212 exhibited insecticidal activities having atleast 80% mortality.

Test Example 5 Small Brown Planthopper Control Test

Rice seedlings grown in pots were subjected to the foliar application ofsolutions of the inventive compounds at a predetermined concentrationprepared to 50% acetone/water (containing 0.05% Tween 20). The treatedseedlings were air dried, following which second-instar larvae werereleased onto the seedlings. The seedlings and larvae were then held inan incubation chamber at 25° C. (16-hour period of light, 8-hour darkperiod). Three days after released, the numbers of live and dead insectswere counted, and the mortality was calculated from the followingformula. This was a two-replication test.Mortality(%)=[number of dead insects/(number of live insects+number ofdead insects)]×100

From these results, with 100 ppm foliar application, Compounds 212, 213,215, 216, 227, 229 and 230 exhibited insecticidal activities having atleast 80% mortality.

Test Example 6 Brown Rice Planthopper Control Test

Rice seedlings grown in pots were subjected to the foliar application ofsolutions of the inventive compounds at a predetermined concentrationprepared to 50% acetone/water (containing 0.05% Tween 20). The treatedseedlings were air dried, following which second-instar larvae werereleased onto the seedlings. The seedlings and larvae were then held inan incubation chamber at 25° C. (16-hour period of light, 8-hour darkperiod). Six days after released, the numbers of live and dead insectswere counted, and the mortality was calculated from the followingformula. This was a two-replication test.Mortality(%)=[number of dead insects/(number of live insects+number ofdead insects)]×100

From these results, with 100 ppm foliar application, Compounds 1, 2, 3,6, 7 and 8 exhibited insecticidal activities having at least 80%mortality.

Test Example 7 White-Backed Rice Planthopper Control Test

Rice seedlings grown in pots were subjected to the foliar application ofsolutions of the inventive compounds at a predetermined concentrationprepared to 50% acetone/water (containing 0.05% Tween 20). The treatedseedlings were air dried, following which second-instar larvae werereleased onto the seedlings. The seedlings and larvae were then held inan incubation chamber at 25° C. (16-hour period of light, 8-hour darkperiod). Four days after released, the numbers of live and dead insectswere counted, and the mortality was calculated from the followingformula. This was a two-replication test.Mortality(%)=[number of dead insects/(number of live insects+number ofdead insects)]×100

From these results, with 100 ppm foliar application, Compound 1exhibited an insecticidal activity having at least 80% mortality.

Test Example 8 Green Rice Leafhopper Control Test

Rice seedlings grown in pots were subjected to the foliar application ofsolutions of the inventive compounds at a predetermined concentrationprepared to 50% acetone/water (containing 0.05% Tween 20). The treatedseedlings were air dried, following which second-instar larvae werereleased onto the seedlings. The seedlings and larvae were then held inan incubation chamber at 25° C. (16-hour period of light, 8-hour darkperiod). Four days after released, the numbers of live and dead insectswere counted, and the mortality was calculated from the followingformula. This was a two-replication test.Mortality(%)=[number of dead insects/(number of live insects+number ofdead insects)]×100

From these results, with 100 ppm foliar application, Compounds 1 and 212exhibited insecticidal activities having at least 80% mortality.

Test Example 9 Greenhouse Whitefly Control Test

Adult greenhouse whiteflies were released onto cucumber plants grown inpots, and allowed to laid eggs overnight. One day after the start ofoviposition, the adults were removed, and the plants and eggs were heldin an incubation chamber at 25° C. (16-hour period of light, 8-hour darkperiod). Three days after the end of oviposition, leaf discs 2.0 cm indiameter were cut from the cucumber plants and, after confirmingoviposition thereon, the leaf discs were sprayed with solutions of theinventive compounds at a predetermined concentration prepared to 50%acetone/water (containing 0.05% Tween 20). After spraying, the treatedleaf discs were held in an incubation chamber at 25° C. (16-hour periodof light, 8-hour dark period). Fourteen days after spraying, the numbersof live and dead insects were counted, and the mortality was calculatedfrom the following formula. This was a two-replication test.Mortality(%)=[(number of oviposited eggs−number of live insects)/numberof oviposited eggs]×100

From these results, with 100 ppm foliar application, Compounds 212, 229and 230 exhibited high insecticidal activities having at least 80%mortality.

With foliar application at 20 ppm, Compound 213 exhibited a highinsecticidal activity having at least 80% a mortality.

Test Example 10-1 Western Flower Thrips Control Test

Leaf discs 2.8 cm in diameter were cut from bean plants grown in pots,and these were sprayed with solutions of the inventive compounds at apredetermined concentration prepared to 50% acetone/water (containing0.05% Tween 20). The treated leaf discs were air dried, following whichfirst-instar larvae were released onto the discs. The leaf discs andlarvae were then held in an incubation chamber at 25° C. (16-hour periodof light, 8-hour dark period). Three days after released, the numbers oflive and dead insects were counted, and the mortality was calculatedfrom the following formula. This was a two-replication test.Mortality(%)=[number of dead insects/(number of live insects+number ofdead insects)]×100

From these results, with 500 ppm foliar application, Compounds 49, 50,85, 86, 90, 91, 93, 94, 104, 107, 108, 114, 128, 131, 135, 137, 140,141, 144, 145, 146, 147, 152, 167, 170, 171, 172, 176, 181, 182, 183,184, 186, 189, 190, 193, 196, 199, 200, 208, 211, 212, 222, 226, 227,229, 230, 231, 237, 240, 242 and 243 exhibited high insecticidalactivities having at least 80% mortality. With 200 ppm foliarapplication, Compounds 1, 2, 3, 6, 7, 8, 9 and 10 exhibited highinsecticidal activities having at least 80% mortality.

Test Example 10-2 Western Flower Thrips Control Test

Leaf discs 2.8 cm in diameter were cut from bean plants grown in pots,and these were sprayed with solutions of the inventive compounds at apredetermined concentration prepared to 50% acetone/water (containing0.05% Tween 20). The treated leaf discs were air dried, following whichfirst-instar larvae were released onto the discs. The leaf discs andlarvae were then held in an incubation chamber at 25° C. (16-hour periodof light, 8-hour dark period). Three days after released, the numbers oflive and dead insects were counted, and the mortality was calculatedfrom the following formula. This was a two-replication test.Mortality(%)=[number of dead insects/(number of live insects+number ofdead insects)]×100

From these results, with 100 ppm foliar application, Compounds 2, 3, 6,7, 8, 9, 10, 90, 91, 104, 128, 137, 186, 193, 212, 213, 216 and 238exhibited high insecticidal activities having at least 80% mortality.

Test Example 11 Rice Leaf Bug Control Test

Wheat seedling shoots four days after sowing were immersed for 30seconds in solutions of the inventive compounds at a predeterminedconcentration prepared to 50% acetone/water (containing 0.05% Tween 20).The treated seedlings were air-dried, then each was placed in a glasscylinder and two second-instar rice leaf bug larvae were released withinthe same glass cylinder. Following release of the insects, the tube wascapped and held in an incubation chamber at 25° C. (16-hour period oflight, 8-hour dark period). In order to supply water to the wheat plantduring the test, the plant was allowed to take up water from below theglass cylinder. Three days after released, the numbers of live and deadinsects were counted, and the mortality was calculated from thefollowing formula.Mortality(%)=[number of dead insects/(number of live insects+number ofdead insects)]×100

From these results, with 50 ppm foliar application, Compounds 132, 141,144, 183, 184, 189, 190, 192, 193, 194, 212, 227, 229, 230, 231, 233,236, 239, 242 and 243 exhibited high insecticidal activities having atleast 80% mortality.

Test Example 12 Brown-Winged Green Bug Control Test

Young apples that had been collected in the field were sprayed withsolutions of the inventive compounds at a predetermined concentrationprepared to 50% acetone/water (containing 0.05% Tween 20). The treatedfruits were air-dried, placed in plastic cups and two adult brown-wingedgreen bugs were released into each cup. Following release of theinsects, the fruits and insects were held in an incubation chamber at25° C. (16-hour period of light, 8-hour dark period). Six days afterreleased, the numbers of live and dead insects were counted, and themortality was calculated from the following formula.Mortality(%)=[number of dead insects/(number of live insects+number ofdead insects)]×100

From these results, with 50 ppm foliar application, Compound 212exhibited a high insecticidal activity having at least 80% mortality.

Test Example 13 Rice Leaf Beetle Control Test

The inventive compounds prepared to a predetermined concentration inacetone were locally applied in an amount of 1 μL (per insect) to thebacks of field-collected adult beetles using a microsyringe. Followingchemical treatment, the beetles were transferred to rice seedlings, withfive beetles being placed on each plant, and the seedlings and beetleswere held in an incubation chamber at 25° C. (16-hour period of light,8-hour dark period). Forty-eight hours after treatment, the numbers oflive and dead insects were counted, and the mortality was calculatedfrom the following formula.Mortality(%)=[number of dead insects/(number of live insects+number ofdead insects)]×100

From these results, at a dosage of 0.5 μg/insect, Compounds 1, 8 and 212exhibited high insecticidal activities having at least 80% mortality.

Test Example 14 House Fly Control Test

The inventive compounds prepared to a predetermined concentration inacetone were applied in an amount of 1 μL (per insect) to the backs ofadult female flies raised indoors. Following chemical treatment, theflies were transferred to plastic cups, with five flies being placed ineach cup, and held in an incubation chamber at 25° C. (16-hour period oflight, 8-hour dark period). Twenty-four hours after treatment, the stateof knockdown among the flies was observed, and the knockdown rate wascalculated from the following formula. The test was carried out as tworeplications.Knockdown rate(%)=[number of knocked down insects/(number of liveinsects+number of knocked down insects)]×100

From these results, at a dosage of 2 μg/insect, Compounds 33, 212, 213,214 and 216 exhibited high insecticidal effects having a knockdown rateof at least 80%. Root Immersion Treatment Test

Test Example 15 Small Brown Planthopper Control Test

Wheat seedling roots 48 hours after sowing were treated with solutionsof the inventive compounds at a predetermined concentration prepared to10% acetone/water. After allowing the roots to absorb the chemical for72 hours, ten second-instar small brown planthopper larvae were releasedonto each seedling. The treated seedlings and larvae were then held inan incubation chamber at 25° C. (16-hour period of light, 8-hour darkperiod). Four days after released, the numbers of live and dead insectswere counted, and the mortality was calculated from the followingformula. The test was carried out as two replications.Mortality(%)=[number of dead insects/(number of live insects+number ofdead insects)]×100

From these results, at a dosage of 20 μg/seedling, Compounds 212, 213,215, 216, 222, 223, 226, 227, 228, 230, 231, 233, 234, 235, 237, 212,213, 214, 215, 216, 222, 223, 227, 228, 229, 231, 233, 234, 235, 237,238, 239, 240 and 241 exhibited high insecticidal activities having atleast 80% mortality. Soil Drenching Treatment Tests

Test Example 16 Small Brown Planthopper Control Test

Rice seedlings grown in pots were subjected to soil drenching treatmentwith solutions of the inventive compounds at a predeterminedconcentration prepared to 10% acetone/water. Three days followingtreatment, ten second-instar small brown planthopper larvae werereleased onto each seedling. The treated seedlings and larvae were thenheld in an incubation chamber at 25° C. (16-hour period of light, 8-hourdark period). Three days after released, the numbers of live and deadinsects were counted, and the mortality was calculated from thefollowing formula. The test was carried out as two replications.Mortality(%)=[number of dead insects/(number of live insects+number ofdead insects)]×100

From these results, at a dosage of 0.05 mg/seedling, Compounds 212, 227,229, 231, 233, 237, 238, 239, 242 and 243 exhibited high insecticidalactivities having at least 80% mortality, and at a dosage of 0.005mg/seedling, Compound 212 exhibited a high insecticidal activity having95% mortality.

Test Example 17 White-Backed Rice Planthopper Control Test

Rice seedlings grown in pots were subjected to soil drenching treatmentwith solutions of the inventive compounds at a predeterminedconcentration prepared to 10% acetone/water. Three days followingtreatment, ten second-instar white-backed rice planthopper larvae werereleased onto each seedling. The treated seedlings and larvae were thenheld in an incubation chamber at 25° C. (16-hour period of light, 8-hourdark period). Three days after released, the numbers of live and deadinsects were counted, and the mortality was calculated from thefollowing formula. The test was carried out as two replications.Mortality(%)=[number of dead insects/(number of live insects+number ofdead insects)]×100

From these results, at a dosage of 0.05 mg/seedling, Compounds 212, 227,229 and 231 exhibited high insecticidal activities having at least 80%mortality.

Test Example 18 Rice Water Weevil Control Test

Rice seedlings grown in pots were subjected to soil drenching treatmentwith solutions of the inventive compounds at a predeterminedconcentration prepared to 10% acetone/water. Two days after treatment,five adult rice water weevils were released onto each seedling. Theseedlings and insects were then held in an incubation chamber at 25° C.(16-hour period of light, 8-hour dark period). Three days afterreleased, the numbers of live and dead insects were counted, and themortality was calculated from the following formula. The test wascarried out as two replications.Mortality(%)=[number of dead insects/(number of live insects+number ofdead insects)]×100

From these results, at a dosage of 0.1 mg/seedling, Compound 212exhibited a high insecticidal activity having at least 80% mortality.

Effects on Pests Having a Low Susceptibility to Insecticides TestExample 19 Brown Rice Planthopper Control Test

Rice seedlings grown in pots were subjected to soil drenching treatmentwith solutions of the inventive compounds at a predeterminedconcentration prepared to 10% acetone/water. Three days after treatment,ten second-instar brown rice planthopper larvae having a lowsusceptibility to insecticides were released onto each seedling. Theseedlings and insects were then held in an incubation chamber at 25° C.(16-hour period of light, 8-hour dark period). Three days afterreleased, the numbers of live and dead insects were counted, and themortality was calculated from the following formula. The test wascarried out as two replications.Mortality(%)=[number of dead insects/(number of live insects+number ofdead insects)]×100

The pests used in this test were insects that had been raised indoorsfor successive generations over a long period of time (susceptibleline), and insects that had been raised indoors for successivegenerations after being collected (I) in 2007 within Kumamoto Prefectureand (II) in 2005 within Fukuoka Prefecture (field-collected lines).

As a result, Compound 212 exhibited a mortality of 100% on all the linesin treatment at a dosage of 0.05 mg/seedling, and exhibited a mortalityof at least 90% on all the lines at a dosage of 0.005 mg/seedling. Bycontrast, when applied at a dosage of 0.05 mg/seedling, imidaclopridexhibited a mortality of 100% in the susceptible line and mortalities of40% on (I) and 60% on (II).

From these results, Compound 212 exhibited a high insecticidal activityagainst brown rice planthoppers having a low susceptibility toimidacloprid.

Test Example 20 Small Brown Planthopper Control Test

Rice seedlings grown in pots were subjected to soil drenching treatmentwith solutions of the inventive compounds at a predeterminedconcentration prepared to 10% acetone/water. Three days after treatment,ten second-instar small brown planthopper larvae having a lowsusceptibility to insecticides were released onto each seedling. Theseedlings and insects were then held in an incubation chamber at 25° C.(16-hour period of light, 8-hour dark period). Three days afterreleased, the numbers of live and dead insects were counted, and themortality was calculated from the following formula. The test wascarried out as two replications.Mortality(%)=[number of dead insects/(number of live insects+number ofdead insects)]×100

The pests used in this test were insects that had been raised indoorsfor successive generations over a long period of time (susceptibleline), and insects that had been raised indoors for successivegenerations after being collected in 2006 within Kumamoto Prefecture(field-collected line).

As a result, Compound 212 exhibited a mortality of 100% on both lines ata dosage of 0.01 mg/seedling, and exhibited a mortality of at least 90%on both lines at a dosage of 0.005 mg/seedling. By contrast, whenapplied at a dosage of 0.01 mg/seedling, imidacloprid exhibited amortality of 100% in the susceptible line and a mortality of 50% in thefield-collected line. When applied at a dosage of 0.01 mg/seedling,fipronil exhibited a mortality of 100% in the susceptible line and amortality of 70% in the field-collected line.

From these results, Compound 212 exhibited a high insecticidal activityagainst small brown planthoppers having a low susceptibility toimidacloprid and fipronil.

Test Example 21 In Vitro Metabolic Tests of Compound 212 andImidacloprid Using House Fly Crude Enzyme Extract

As mentioned in Pest Management Science, 59(3), 347-352 (2003) and theJournal of Pesticide Science, 29(2), 110-116 (2004), imidacloprid isknown to be inactivated by incurring oxidative metabolism, which isthought to be one mechanism of acquiring resistance to this agent. Thefollowing experiment was carried out to confirm the effects in pestswhich have acquired such resistance.

An amount of 10 mL of a potassium phosphate buffer solution (pH 7.4,containing 1 mM EDTA) was added to adult house flies (0.645 g), and theflies were thoroughly homogenized in a Physcotron (Niti-On Medical andPhysical Instruments Manufacturing Co.). The homogenate was thencentrifuged at 10,000 g for 15 minutes. The resulting supernatant wasadditionally centrifuged at 100,000 g for 60 minutes, giving aprecipitate. The precipitate was dissolved in 1 mL of a potassiumphosphate buffer, and the resulting solution was used as the crudeenzyme extract. The enzyme extraction operations were all carried out onice or at 4° C.

The reagents were mixed in the following proportions within a 1.5 mLtube, and the reaction was effected at 25° C. for 40 hours. Followingthe reaction, 1 mL of acetone was added and the mixture was stirred,following which the precipitate that formed was centrifuged at 12,000rpm for 5 minutes. The supernatant acetone was distilled off, and theprecipitate was injected into a liquid chromatograph-mass spectrometer(LC/MS) and analysis was carried out.

Above crude enzyme extract: 300 μL

DMSO solution of compound: 5 μL

Glucose 6 phosphoric acid solution: 5 μL

NADP⁺ solution: 5 μL

Glucose 6 phosphoric acid dehydrogenase solution: 5 μL

Potassium phosphate buffer (pH 7.4, containing 1 mM EDTA): 180 μL

<Analysis Conditions>

Column: Capcell Pak C18MG

Mobile phase composition:

0 to 3 minutes: 85% water, 5% acetonitrile, 10% aqueous formic acidsolution (0.1% v/v)

3 to 30 minutes: 85→25% water, 5→65% acetonitrile, 10% aqueous formicacid solution (0.1% v/v)

30.1 to 36 minutes: 90% acetonitrile, 10% aqueous formic acid solution(0.1% v/v)

Column temperature: 40° C.

Flow rate: 0.35 mL/min

Injected amount: 100 μL

UV wavelength: Compound 212: 325 nm

Imidacloprid: 300 nm

As a result, the sum of the surface area percentages for the metaboliteswas 0.08% in the case of Compound No. 212 and 2.55% in the case ofimidacloprid, indicating that the amount of metabolites of Compound No.212 was lower than the amount of metabolites of imidacloprid. The aboveresults suggest that Compound 212 can effectively control even resistantpests which metabolically deactivate imidacloprid.

Control Effects on Animal Parasitic Pests Test Example 21 Tick(Haemaphysalis Longicornis) Control Test

Glass vials having a capacity of 4 mL were each filled with 30 μL of anacetone solution containing 200 ppm or 10 ppm of the respectivecompounds. These filled vials were placed on a shaker and air-driedwhile being spun, thereby forming dry films of the compounds on theinner walls of the vials. After the vials had been dried for at least 24hours, ten larval ticks (Haemaphysalis longicornis) were released intoeach vial, following which the vials were capped. The vials were thenleft at rest in an incubation chamber at 25° C., 85% humidity andcomplete darkness. One day after released, the numbers of live and deadticks were counted, and the mortality was calculated from the followingformula. This test was carried out as two replications.Mortality(%)=[number of dead ticks/(number of live ticks+number of deadticks)]×100

As a result, at a dosage of 200 ppm, Compounds 1, 2, 3, 6, 7, 8, 9, 10,11, 15, 18, 19, 20, 21, 39, 41, 42, 43, 45, 49, 50, 53, 58, 61, 72, 86,88, 89, 91, 92, 93, 94, 96, 97, 101, 102, 105, 107, 108, 109, 111, 112,114, 115, 119, 120, 130, 131, 132, 135, 137, 138, 165, 196, 199, 200,204, 212, 213 and 214 exhibited tickcidal effects having at least 80%mortality.

At a dosage of 10 ppm, Compounds 1, 2, 3, 6, 7, 8, 9, 10, 18, 19, 42,43, 58, 88, 91, 93, 94, 165, 196, 208, 212, 213 and 214 exhibitedtickcidal effects having at least 80% mortality.

In similar tests, the mortality from treatment with 10 ppm ofimidacloprid was 4%.

Test Example 22 Tick (Haemaphysalis longicornis) Control Test on BodySurface of Mouse

Ventral fur was shaved from an area having a diameter of about 2 cm inmice (ICR, 5-week-old males), and a 15 mL polystyrene conical tube cutto a length of about 1.5 cm was attached to the shaved area usinginstant glue.

An amount of 20 μL of a 1,000-fold dilution of the pest control agentprepared in the same way as in Formulation Example 11 was added dropwiseonto the body surface of the mice within the attached tube. After thesolution was allowed to dry thoroughly, ten or more larval ticks(Haemaphysalis longicornis) were released into the tube, which was thencapped. Three days after released, the numbers of live and dead tickswere counted, and the mortality was calculated from the followingformula.Blood-feeding inhibition(%)=100−[number of feeding ticks/(number of liveticks+number of dead ticks)]×100

As a result, Compound 212 below exhibited a blood-feeding inhibition of91%.

Test Example 23 Effects on Canine Heartworm

The activities of the compounds were evaluated based on changes in themotility of microfilariae in canine heartworm. The respective compoundswere dissolved in a RPMI1640 liquid culture medium to a concentration of3.13 ppm, following which about 20 canine heartworm microfilariae wereplaced in each culture fluid and cultured at 37° C. The motility of thecanine heartworm microfilariae was observed for 48 hours following thestart of culturing, and the activities of the compounds were ratedaccording to the following criteria.

Criteria A: At least two-thirds of the heartworms died

-   -   B: Substantially all the heartworms were affected in some way,        or at least one-third died    -   C: No influence, or less than one-third of the heartworms died

As a result, at a dosage of 3.13 ppm, Compounds 1, 2, 6, 7, 8, 9 and 10had a microfilaricidal effect at or higher than level B.

The microfilaricidal effects of Compound Nos. 212, 227, 229, 231, 237,238, 239, 242 and 243, which are especially preferred compoundsaccording to the invention, are summarized in Table 12.

TABLE 12 Insecticidal effects (mortality) in various pests WesternDiamondback Common flower moth cutworm thrips second- third- Cottonaphid first- instar instar first-instar instar larvae larvae larvaelarvae Compound Foliar application (ppm) No. 500 100 20 500 100 500 10020 5 1.25 500 100 20 212 100 100 100 100 30 100 100 100 95 100 100 10065 227 100 100 100 100 56 100 100 100 100 95 90 65 229 100 100 40 100 30100 100 100 95 80 100 60 231 100 100 0 0 100 100 74 85 55 237 100 100100 33 100 100 85 90 238 100 60 0 100 100 100 100 95 239 100 100 100 90100 100 100 40 242 100 100 60 100 100 80 35 100 76 243 100 100 10 100100 100 80 100 Insecticidal effects (mortality) in various pests Smallbrown planthopper second-instar larvae Foliar Soil drenching applicationtreatment Wheat root immersion treatment Compound (ppm) (mg/pot)(mg/seedling) No. 100 5 1.25 0.313 0.05 0.01 0.005 0.002 20 2 0.5 0.250.125 212 100 100 75 100 100 95 85 100 100 100 100 100 227 100 90 100 75100 75 50 229 95 100 100 30 100 100 75 231 100 100 100 70 100 75 25 237100 75 100 100 50 238 100 100 33 100 100 100 100 239 100 80 30 100 100100 100 242 100 100 100 100 243 100 100 100 100 Insecticidal effects(mortality) in various pests Brown rice planthopper second- instar Riceleaf Adult Small brown planthopper larvae bug, house second-instarlarvae Soil second- flies Wheat root drenching instar Dosage immersiontreatment treatment larvae 3 mg/ Compound (mg/seedling) (mg/pot) or 4DAA fly No. 0.063 0.031 0.016 0.0078 0.05 0.02 50 10 2 2 212 100 100 5050 100 100 100 100 100 100 227 100 100 83 229 25 100 100 100 231 100 23767 238 25 100 239 100 242 100 243 100

In addition, the effects against pests having a low susceptibility toinsecticides by Compound Nos. 212, 227, 229, 231, 237, 238, 239, 242 and243, which are especially preferred compounds according to theinvention, are summarized in Table 13.

TABLE 13 Brown rice planthopper, Kumamoto low susceptibility Small brownplanthopper (rice soil (rice soil drenching) drenching) 0.05 mg/ 0.01mg/ 0.005 mg/ 0.002 mg/ 0.05 mg/ 0.005 mg/ pot pot pot pot pot pot 212100 100 95 85 100 90 227 90 100 75 229 100 100 30 231 100 100 70 237 10075 238 100 100 33 239 100 80 30 242 100 243 100 Comparative Example 2 20(Patent Document 6, Compound 20) Comparative Example 3 10 (PatentDocument 4, Compound 2) Comparative Example 4 100 20 45 (Patent Document5, Example 4) Comparative Example 5 95 15 25 (Patent Document 5, Example3) Comparative Example 6 100 20 25 (Patent Document 5, Example 5)Comparative Example 7 63 5 20 (Patent Document 5, Example 7) ComparativeExample 8 20 (Patent Document 5, Example 6)

INDUSTRIAL APPLICABILITY

The amine derivatives of the present invention have excellentinsecticidal effects against the diamondback moth, the common cutworm,the cotton aphid, the small brown planthopper, the brown riceplanthopper, the green rice leafhopper, the hard-bodied tickHaemaphysalis longicornis, and many other pests. Also, they are able toexhibit strong effects even against insects having a low insecticidesusceptibility, particularly delphacid planthoppers. Moreover, they areeffective also in treating soil and plant cultivation media and, becausethey are able to mitigate the chances of worker exposure to chemicals,can be safely used to control pests. Therefore, the present invention iscapable of being highly beneficial in the field of pest control.

The invention claimed is:
 1. A pest control composition comprising atleast one compound of the following formula (I) or a salt thereof

(wherein Ar is a pyridyl group which may be substituted with one or morehalogen atoms, C₁₋₄ alkyl groups which may be substituted with halogenatoms, alkyloxy groups which may be substituted with halogen atoms,hydroxyl groups, cyano groups and nitro groups; R₁ is a hydrogen atom ora C₁₋₆ alkyl group; R₂ is a cyano group; R₃ is a C₁₋₈ alkylene groupwhich may be substituted with a halogen atom, a C₂₋₈ alkenylene groupwhich may be substituted with a halogen atom, a C₂₋₈ alkynylene groupwhich may be substituted with a halogen atom, a phenylene group whichmay be substituted, or a 5- or 6-membered heterocyclic divalent groupwhich may be substituted; and R₄ is SR₅, SOR₅, SO₂R₅, N—CO—OR₈,N—CO—SR₈, N—CS—OR₈, N—CS—SR₈, N—O—CO—R₈, O—CO—R₈, O—CO—OR₈, O—CO—SR₈,O—CS—OR₈, O—CS—SR₈, S—CS—OR₈, S—CS—SR₈, S—CO—OR₈, S—CO—SR₈, S—CS—R₈,O—CO—NR₉R₁₀, O—CS—NR₉R₁₀, S—CO—NR₉R₁₀ or S—CS—NR₉R₁₀; wherein R₅ is aC₁₋₆ alkyl group which may be substituted with a halogen atom, an arylgroup which may be substituted with a halogen atom or an aralkyl groupwhich may be substituted with a halogen atom; R₈ is a C₁₋₆ alkyl groupwhich may be substituted, the substituent which may be substituted beinga halogen atom, a C₁₋₄ alkyloxycarbonyl group, a C₁₋₄ alkylcarbonylgroup, a benzoyl group which may be substituted with a halogen atom or aC₁₋₄ alkyl group which may be substituted with a halogen atom, a C₁₋₄alkyloxy group or a C₁₋₄ alkylthio group; R₉ and R₁₀ are eachindependently a hydrogen atom, a formyl group, a C₁₋₆ alkyl group whichmay be substituted with a halogen atom, a C₁₋₆ alkylcarbonyl group inwhich the alkyl moiety may be substituted with a halogen atom, a C₁₋₆alkylcarbonyloxy group in which the alkyl moiety may be substituted witha halogen atom, a phenyl group which may be substituted (the substituentwhich may be substituted being a halogen atom, a C₁₋₄ alkyl group whichmay be substituted with a halogen atom, or a C₁₋₄ alkyloxy group whichmay be substituted with a halogen atom), or a benzyl group which may besubstituted (the substituent which may be substituted being a halogen, aC₁₋₄ alkyl group which may be substituted with a halogen or a C₁₋₄alkyloxy group which may be substituted with a halogen); or R₉ and R₁₀together form a 3- to 10-membered heterocycloalkyl ring containing atleast one nitrogen atom; or N, R₉ and R₁₀ together form a 5- or6-membered aromatic heterocyclic ring containing at least one nitrogenatom, and a carrier suitable for pest control.
 2. The pest controlcomposition according to claim 1, wherein Ar in formula (I) is a6-chloro-3-pyridyl group.
 3. The pest control composition accordingclaim 1, which has a pest control activity on at least one type of pestselected from the group consisting of lepidopterous pests, hemipterouspests, thysanopterous pests, dipterous pests, coleopterous pests, animalparasitic fleas and ticks, and canine heartworms.
 4. The pest controlcomposition according to claim 1, wherein the pest is anagricultural/horticultural pest or an animal parasitic pest.
 5. The pestcontrol composition according to claim 1, wherein the pest is apesticide-resistant pest.
 6. An amine derivative of the followingformula (I) or a salt thereof

wherein Ar is a pyridyl group which may be substituted with one or morehalogen atoms, C₁₋₄ alkyl groups which may be substituted with halogenatoms, alkyloxy groups which may be substituted with halogen atoms,hydroxyl groups, cyano groups and nitro groups; R₁ is a hydrogen atom ora C₁₋₆ alkyl group; R₂ is a cyano group; R₃ is a C₁₋₈ alkylene groupwhich may be substituted with a halogen atom, a C₂₋₈ alkenylene groupwhich may be substituted with a halogen atom, a C₂₋₈ alkynylene groupwhich may be substituted with a halogen atom, a phenylene group whichmay be substituted, or a 5- or 6-membered heterocyclic divalent groupwhich may be substituted; and R₄ is SR₅, SOR₅, SO₂R₅, N—CO—OR₈,N—CO—SR₈, N—CS—OR₈, N—CS—SR₈, N—O—CO—R₈, O—CO—R₈, O—CO—OR₈, O—CO—SR₈,O—CS—OR₈, O—CS—SR₈, S—CS—OR₈, S—CS—SR₈, S—CO—OR₈, S—CO—SR₈, S—CS—R₈,O—CO—NR₉R₁₀, O—CS—NR₉R₁₀, S—CO—NR₉R₁₀ or S—CS—NR₉R₁₀; wherein R₅ is aC₁₋₆ alkyl group which may be substituted with a halogen atom, an arylgroup which may be substituted with a halogen atom or an aralkyl groupwhich may be substituted with a halogen atom; R₈ is a C₁₋₆ alkyl groupwhich may be substituted, the substituent which may be substituted beinga halogen atom, a C₁₋₄ alkyloxycarbonyl group, a C₁₋₄ alkylcarbonylgroup, a benzoyl group which may be substituted with a halogen atom or aC₁₋₄ alkyl group which may be substituted with a halogen atom, a C₁₋₄alkyloxy group or a C₁₋₄ alkylthio group; R₉ and R₁₀ are eachindependently a hydrogen atom, a formyl group, a C₁₋₆ alkyl group whichmay be substituted with a halogen atom, a C₁₋₆ alkylcarbonyl group inwhich the alkyl moiety may be substituted with a halogen atom, a C₁₋₆alkylcarbonyloxy group in which the alkyl moiety may be substituted witha halogen atom, a phenyl group which may be substituted (the substituentwhich may be substituted being a halogen atom, a C₁₋₄ alkyl group whichmay be substituted with a halogen atom, or a C₁₋₄ alkyloxy group whichmay be substituted with a halogen atom), or a benzyl group which may besubstituted (the substituent which may be substituted being a halogen, aC₁₋₄ alkyl group which may be substituted with a halogen or a C₁₋₄alkyloxy group which may be substituted with a halogen); or R₉ and R₁₀together form a 3- to 10-membered heterocycloalkyl ring containing atleast one nitrogen atom; or N, R₉ and R₁₀ together form a 5- or6-membered aromatic heterocyclic ring containing at least one nitrogenatom.
 7. The amine derivative or a salt thereof according to claim 6,wherein Ar in formula (I) is a 6-chloro-3-pyridyl group.
 8. The aminederivative or a salt thereof according to claim 6, which has a pestcontrol activity on at least one type of pest selected from the groupconsisting of lepidopterous pests, hemipterous pests, thysanopterouspests, dipterous pests, coleopterous pests, animal parasitic fleas andticks, and canine heartworms.
 9. A method for controlling pests,comprising the step of using the pest control composition according toclaim 1 or the amine derivative or a salt thereof according to claim 6.10. A method for controlling agricultural/horticultural pests,comprising the step of treating plant seeds, roots, tubers, bulbs,rhizomes, soil, a nutrient solution in nutriculture, a solid culturemedium in nutriculture, or a carrier for growing plants, with the pestcontrol composition according to claim 1 or the amine derivative or asalt thereof according to claim 6, thereby inducing the compound offormula (I) or the amine derivative or salt thereof to penetrate andtranslocate into the plants.
 11. The method according to claim 9,wherein the pest is an agricultural/horticultural pest or an animalparasitic pest.
 12. The method according to claim 9, wherein the pest isa pesticide-resistant pest.